Ming Luo's research while affiliated with Georgia State University and other places
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Publications (170)
The master transcriptional regulator PU.1/Spi-1 engages DNA sites with affinities spanning multiple orders of magnitude. To elucidate this remarkable plasticity, we have characterized 22 high-resolution co-crystallographic PU.1/DNA complexes across the addressable affinity range in myeloid gene transactivation. Over a purine-rich core (such as 5'-G...
Accumulating evidence has demonstrated that the overexpression of and the loss of tumor suppressor genes contribute to the aggressiveness, poor prognosis, and poor response to treatment associated with advanced cancer. Overexpression and activation of the MDM2 and NFAT1 oncogenes frequently occur in human cancer and is associated with invasive and...
Like other negative-strand RNA viruses (NSVs) such as influenza and rabies, vesicular stomatitis virus (VSV) has a three-layered organization: a layer of matrix protein (M) resides between the glycoprotein (G)-studded membrane envelope and the nucleocapsid, which is composed of the nucleocapsid protein (N) and the encapsidated genomic RNA. Lack of...
Evidence suggests that increased microRNA-155 (miR-155) expression in immune cells enhances anti-tumor immune responses. However, given the reported association of miR-155 to tumorigenesis in various cancers, a debate is provoked on whether miR-155 is oncogenic or tumor suppressive. We aimed to interrogate the impact of tumor miR-155 expression, pa...
Mouse double minute 2 homolog (MDM2) is an E3 ubiquitin‐protein ligase that is involved in the transfer of ubiquitin to p53 and other protein substrates. The expression of MDM2 is elevated in cancer cells and inhibitors of MDM2 showed potent anticancer activities. Many inhibitors target the p53 binding domain of MDM2. However, inhibitors such as In...
Significance
Unlike fellow nonsegmented negative-strand RNA viruses, exemplified by the devastating Nipah, Ebola, rabies, and measles viruses, vesicular stomatitis virus (VSV) can be considered beneficial, as it is widely used as a vector for anticancer therapy and vaccine development. In these RNA viruses, transcription and replication of the vira...
Like other negative-strand RNA viruses (NSVs) such as influenza and rabies, vesicular stomatitis virus (VSV) has a three-layered organization: a layer of matrix protein (M) resides between the membrane envelope, studded by glycoprotein (G), and the nucleocapsid, composed of the nucleocapsid protein (N) and the encapsidated genomic RNA. Lack of in s...
Background
The immunosuppressive microenvironment in pancreatic ductal adenocarcinoma is a major factor that limits the benefits of immunotherapy, especially immune checkpoint blockade. One viable strategy for reverting the immunosuppressive conditions is the use of an oncolytic virus (OV) in combination with other immunotherapy approaches. Infecti...
Negative strand RNA viruses (NSVs) include many important human pathogens, such as influenza virus, Ebola virus, and rabies virus. One of the unique characteristics that NSVs share is the assembly of the nucleocapsid and its role in viral RNA synthesis. In NSVs, the single strand RNA genome is encapsidated in the linear nucleocapsid throughout the...
MicroRNA 155 (miR-155) plays important roles in the regulation of the development and functions of a variety of immune cells. We previously revealed a vital role of miR-155 in regulating the function of dendritic cells (DCs) in breast cancer. miR-155 deficiency in DCs impaired their maturation, migration, cytokine production, and ability to activat...
Despite reports of successful clinical cases, many tumors appear to resist infection by oncolytic viruses (OVs). To circumvent this problem, an armed vesicular stomatitis virus was constructed by inserting a transgene to express Smac/DIABLO during virus infection (VSV-S). Endogenous Smac in HeLa cells was diminished during wtVSV infection, whereas...
Negative-strand RNA viruses (NSVs) include the most pathogenic viruses known. New methods to monitor their evolutionary trends are urgently needed for the development of antivirals and vaccines. The protein translation machinery of the host cell is currently recognized as a main genomic regulator of RNA virus evolution, which works especially well...
Subtomographic averages of gB without imposing symmetry.
(A, B) Subtomographic averages of gB in its postfusion conformation without imposing symmetry viewed from side (A) and top (B).
(C, D) Subtomographic averages of gB in its prefusion conformation without imposing symmetry viewed from side (C) and top (D).
(TIF)
Comparison of tomograms obtained with and without VPP.
(A~C) A slice (A) and zoom-in envelope regions (B, C) of a tomogram reconstructed from tilt series obtained with VPP, showing greatly improved contrast that is sufficient to distinguish columnar tree-shaped (“postfusion”) gB (yellow arrows in B) from the Christmas tree-shaped (prefusion) gB (re...
Direct comparisons of the averaged map and fitted pseudoatomic model between prefusion HCMV gB and previous “short-form” HSV-1 gB.
(A) Christmas tree-shaped prefusion gB on HCMV virion (this study), reviewed from its side and top, as in Figs 3 and 5.
(B) “Short-form” gB of HSV-1 [27] showing as in (A), colored surface (upper panel) and superpositio...
MDFF-simulated prefusion gB structure, colored as [16], is superimposed with two other symmetric copies (gray ribbon) in the subtomographic average of the Christmas tree-shaped density (semi-transparent gray).
(AVI)
An example of aligned tilt series obtained without VPP.
(Scale bar: 100nm.)
(AVI)
Surface rendering of the subtomographic average of “postfusion” gB (yellow) and associated membrane bilayer (blue).
(AVI)
An example of aligned tilt series obtained with VPP.
(Scale bar: 100nm.)
(AVI)
Surface rendering of the subtomographic average of prefusion gB (yellow) and associated membrane bilayer (blue).
(AVI)
Slices through a tomogram reconstructed by simultaneous iterative reconstruction technique (SIRT) from tilt series in S1 Movie.
(Scale bar: 100nm.)
(AVI)
Human cytomegalovirus (HCMV) enters host by glycoprotein B (gB)-mediated membrane fusion upon receptor-binding to gH/gL-related complexes, causing devastating diseases such as birth defects. Although an X-ray crystal structure of the recombinant gB ectodomain at postfusion conformation is available, the structures of prefusion gB and its complex wi...
Slices through a tomogram reconstructed by SIRT from tilt series in S3 Movie.
(Scale bar: 100nm.)
(AVI)
Fourier shell correlation (FSC) analyses and resolution comparisons.
(A) FSC coefficients as a function of spatial frequency for the gold-standard resolution determined for final subtomographic averages of prefusion (black) and “postfusion” (red) gB trimers.
(B) FSC coefficients as a function of spatial frequency between subtomographic averages of...
Tomograms and subtomographic averages from tilt series obtained without VPP.
(A, B) Comparison of corresponding slices from CTF-uncorrected (A) and CTF-corrected (B) tomograms. The viral envelope region of the particle indicated by the dashed boxes in (A, red) and (B, yellow) are enlarged, showing that the membrane bilayer is better resolved after...
During viral RNA synthesis of a negative-strand RNA virus, the viral RNA-dependent RNA polymerase (vRdRp) must gain access to the sequestered RNA in the nucleocapsid to use it as the template, but at the same time may not disrupt the nucleocapsid assembly. Our structural and mutagenesis studies showed that a flexible structural motif acts as a pote...
Metabolic reprogramming of cancer cells is essential for tumorigenesis, in which pyruvate kinase M2 (PKM2), the low activity isoform of pyruvate kinase, plays a critical role. Herein, we describe the identification of a nature-product-derived micheliolide (MCL) that selectively activates PKM2 through the covalent binding at residue cysteine424 (C42...
Polyamides have been shown to bind double-stranded DNA by complementing the curvature of the minor groove and forming various hydrogen bonds with DNA. Several polyamide molecules have been found to have potent antiviral activities against papillomavirus, a double-stranded DNA virus. By analogy, we reason that polyamides may also interact with the s...
In the face of increasing drug resistance and the rapidly increasing necessity for practicality in clinical settings, drugs targeting different viral proteins are needed in order to control influenza A and B. A small molecule that tenaciously adheres to the PB2cap binding domain, part of the heterotrimeric RNA polymerase machinery of influenza A vi...
![Figure 6. B-putty drawings [26] of 5WOP Chain A [13], 5EG7 [10], 4ENF...](profile/Amanda-Constantinides/publication/322753434/figure/fig1/AS:614214867644435@1523451644835/B-putty-drawings-26-of-5WOP-Chain-A-13-5EG7-10-4ENF-11-4CB5-and-4CB7-Chain-A_Q320.jpg)
X-ray crystallographic structural determinations of the PB2 cap binding domain (PB2cap) have improved the conformational characterization of the RNA-dependent RNA polymerase machinery (PA, PB2, and PB1) of the influenza virus. Geometrically, the catalytic PB1 subunit resembles the palm of a human hand. PA lies near the thumb region, and PB2 lies ne...
Human hemoglobin (HbA) transports molecular oxygen (O2) from the lung to tissues where the partial pressure of O2 is lower. O2 binds to HbA at the heme cofactor and is stabilized by a distal histidine (HisE7). HisE7 has been observed to occupy opened and closed conformations, and is postulated to act as a gate controlling the binding/release of O2....
The preS antigen of hepatitis B virus (HBV) corresponds to the N-terminal polypeptide in the large (L) antigen in addition to the small (S) antigen. The virus-like particle (VLP) of the S antigen is widely used as a vaccine to protect the population from HBV infection. The presence of the S antigen and its antibodies in patient blood has been used...
In a negative strand RNA virus, the genomic RNA is sequestered inside the nucleocapsid when the viral RNA-dependent RNA polymerase uses it as the template for viral RNA synthesis. It must require a conformational change in the nucleocapsid protein (NP) to make the RNA accessible by the viral polymerase during this process. The structure of an empty...
No abstract is available for this article.
The RNA polymerase of influenza virus consists of three subunits: PA, PB1 and PB2. It uses a unique `cap-snatching' mechanism for the transcription of viral mRNAs. The cap-binding domain of the PB2 subunit (PB2cap) in the viral polymerase binds the cap of a host pre-mRNA molecule, while the endonuclease of the PA subunit cleaves the RNA 10–13 nucle...
Importance:
Negative strand RNA viruses include a diverse set of viral families that infect animals and plants causing serious illness and economic impact. This group of viruses share a common set of functionally conserved proteins that are essential to their replication cycle. Among this set of proteins is the viral polymerase, which performs a u...
During cell entry of an enveloped virus, the viral membrane must be fused with the cellular membrane. The virus envelope has a unique structure consisting of viral proteins and a virus-specific lipid composition, whereas the host membrane has its own structure with host membrane proteins. Compound 136 was previously found to bind in close proximity...
Mumps virus (MuV) encodes a phosphoprotein (P) that is important for viral RNA synthesis. P forms the viral RNA-dependent RNA polymerase with the large protein (L). P also interacts with the viral nucleocapsid protein (NP) and self-associates to form a homotetramer. The P protein consists of three domains, N-terminal domain (PN), oligomerization do...
We have developed a novel, mild, efficient, and scalable protocol for the synthesis of N-protected β-cyano-l-alanine esters or -amides from N-protected l-asparagin. This protocol avoided the use of toxic or unpleasant reagents and was easy to operate in laboratory.
New inhibitors of influenza viruses are needed to combat the potential emergence of novel human influenza viruses. We have identified a class of small molecules that inhibit replication of influenza virus at picomolar concentrations in plaque reduction assays. The compound also inhibits replication of vesicular stomatitis virus. Time of addition an...
The influenza RNA-dependent RNA polymerase is a core enzyme required for both transcription and replication of the virus RNA genome, which makes it a potential drug target for the influenza virus. To detect the feature of cap-dependent transcription of influenza B virus (FluB) polymerase, we determined the crystal structures of the wild-type FluB p...
Significance
In this paper, we reveal several insights into how mumps virus (MuV) replicates its RNA genome. The MuV genomic RNA is packaged by the nucleocapsid protein (N), forming a helical structure called the nucleocapsid. The nucleocapsid is the template for RNA synthesis. MuV genomes cannot be copied unless the viral polymerase (vRdRp) can re...
A series of piperidine-based derivatives were identified as novel and potent inhibitors of influenza virus through structural modification of the original compound that was selected from a high-throughput screen. Various analogues were synthesized and confirmed as inhibitors. The structure-activity relationship (SAR) studies suggested that the ethe...
Significance
Respiratory syncytial virus (RSV) causes major disease in pediatric and elderly patients, urging the development of efficacious therapeutics. This study establishes a recombinant RSV reporter strain for drug discovery and identifies an entry inhibitor class targeting the viral fusion (F) protein. Biochemical, structural, and functional...
Objective
To study the relationship between the human secreted protein stabilin-1−interacting chitinase-like protein (SI-CLP) and rheumatoid arthritis (RA).Methods
The expression of SI-CLP in peripheral blood mononuclear cells (PBMCs) and synovial fluid from patients with RA and the effects of cytokines on SI-CLP expression were examined by Western...
Unlabelled:
The nucleocapsid of a negative-strand RNA virus is assembled with a single nucleocapsid protein and the viral genomic RNA. The nucleocapsid protein polymerizes along the length of the single-strand genomic RNA (viral RNA) or its cRNA. This process of encapsidation occurs concomitantly with genomic replication. Structural comparisons of...
Virus particles are among the biological subjects that were first found to form single crystals. Their atomic structures were solved when X-ray sources became stronger in intensity. Virus crystals have large unit cell dimensions and are generally sensitive to X-ray radiation. However, the high symmetry of virus particles allows the crystal structur...
Confronted with an increasing number of emerging and re-emerging viral pathogens, the identification of novel pathogen-specific and broad-spectrum antivirals has become a major developmental objective. Targeting host factors required for virus replication presents a tangible approach towards novel hits with broadened indication range. However, the...
The phosphoprotein (P) is virally encoded by the Rhabdoviridae and Paramyxoviridae in the order Mononegavirales. P is a self-associated oligomer and forms complexes with the large viral polymerase protein (L), the nucleocapsid protein
(N), and the assembled nucleocapsid. P from different viruses has shown structural diversities even though their es...
All orthobunyaviruses possess three genome segments of single-stranded negative sense RNA that are encapsidated with the virus-encoded
nucleocapsid (N) protein to form a ribonucleoprotein (RNP) complex, which is uncharacterized at high resolution. We report
the crystal structure of both the Bunyamwera virus (BUNV) N–RNA complex and the unbound Schm...
All orthobunyaviruses possess three genome segments of single-stranded negative sense RNA that are encapsidated with the virus-encoded
nucleocapsid (N) protein to form a ribonucleoprotein (RNP) complex, which is uncharacterized at high resolution. We report
the crystal structure of both the Bunyamwera virus (BUNV) N–RNA complex and the unbound Schm...
All orthobunyaviruses possess three genome segments of single-stranded negative sense RNA that are encapsidated with the virus-encoded
nucleocapsid (N) protein to form a ribonucleoprotein (RNP) complex, which is uncharacterized at high resolution. We report
the crystal structure of both the Bunyamwera virus (BUNV) N–RNA complex and the unbound Schm...
PB2 is one of the subunits of the influenza virus heterotrimeric polymerase. By its cap-binding domain (PB2cap), PB2 captures the 5' cap of the host pre-mRNA to generate a capped 5' oligonucleotide primer for virus transcription. The crystal structure of influenza A virus H3N2 PB2cap with bound cap analogue m(7)GTP has been reported previously. To...
Influenza virus RNA-dependent RNA polymerase (RdRp) is a heterotrimer composed of PA, PB1 and PB2 subunits. RdRp is required for both transcription and replication of influenza viral RNA taking place in the nucleus of infected cells. A 'cap-snatching' mechanism is employed to generate a 5'-capped primer for transcription, in which the cap-binding d...
Cell death and differentiation is a monthly research journal focused on the exciting field of programmed cell death and apoptosis. It provides a single accessible source of information for both scientists and clinicians, keeping them up-to-date with advances in the field. It encompasses programmed cell death, cell death induced by toxic agents, dif...
BAR (Bin/amphiphysin/Rvs) domain-containing proteins participate in cellular membrane remodeling. The F-BAR proteins normally
generate low curvature tubules. However, in the PACSIN subfamily, the F-BAR domain from PACSIN 1 and 2 can induce both high
and low curvature tubules. We found that unlike PACSIN 1 and 2, PACSIN 3 could only induce low curva...
The nucleocapsid of vesicular stomatitis virus serves as the genomic template for transcription and replication. The viral genomic RNA is sequestered in the nucleocapsid in every step of the virus replication cycle. The structure of the nucleocapsid and the entire virion revealed how the viral genomic RNA is encapsidated and packaged in the virus....
As all the enveloped viruses, the entry of influenza viruses includes a number of steps in host cell infection. This chapter summarizes the current knowledge of the entry pathway and the role of the fusion protein of influenza virus, hemagglutinin, in this process. Hemagglutinin (HA) is a trimeric glycoprotein that is present in multiple copies in...
Inherently unstable mRNAs contain AU-rich elements (AREs) in the 3′ untranslated regions. Expression of ARE-containing type
I interferon transcripts is robustly induced upon viral infection and rapidly shut off thereafter. Their transient accumulation
is partly mediated through posttranscriptional regulation. Here we show that mouse embryonic fibro...
The genomic RNA of negative-strand RNA viruses, such as vesicular stomatitis virus (VSV), is completely enwrapped by the nucleocapsid
protein (N) in every stage of virus infection. During viral transcription/replication, however, the genomic RNA in the nucleocapsid
must be accessible by the virus-encoded RNA-dependent RNA polymerase in order to ser...
Human secreted protein stabilin-1 interacting chitinase-like protein (SI-CLP) has been identified as a novel member of Glyco_18 domain-containing proteins that is involved in host defense and inflammatory reactions. Efficient secretion of SI-CLP is mediated by its interaction with the endocytic/sorting receptor stabilin-1. SI-CLP is expressed abund...
To gain insight into the structural and functional properties of the vesicular stomatitis virus nucleocapsid-RNA complex (vN-RNA), we analyzed it by treatment with proteolytic enzymes. Chymotrypsin treatment to the vN-RNA results in complete digestion of the C-terminal 86 amino acids of the N protein. The residual chymotrypsin resistant vN-RNA comp...
VSV in 3D
Rhabdoviruses are a family of negative-stranded RNA viruses that includes rabies virus, which have a characteristic bullet shape. Though structures of individual rhabdovirus proteins have been reported, how these are organized into a bullet shape has remained unclear. Now, Ge et al. (p. 689 ) report a cryo-electron microscopy structure of...
PACSIN 1, which is mainly detected in brain tissue, is one of the PACSIN-family proteins involved in endocytosis and recruitment of synaptic vesicles. It binds to dynamin, synaptojanin 1 and N-WASP, and functions in vesicle formation and transport. However, the mechanisms of action of PACSIN 1 in these processes are largely unknown. Here, full-leng...
A concise and modular approach to synthesize a new type of cyclopentene-based diaminocyclitol library from D-serine and L-serine has been developed, and key steps in this synthesis are an aza-Claisen rearrangement, a ring-closing metathesis, and a Baylis-Hillman reaction. The developed chemistry may offer a unique way to investigate the neuraminida...
The negative-strand RNA viruses (NSRVs) are unique because their nucleocapsid, not the naked RNA, is the active template for transcription and replication. The viral polymerase of nonsegmented NSRVs contains a large polymerase catalytic subunit (L) and a nonenzymatic cofactor, the phosphoprotein (P). Insight into how P delivers the polymerase compl...
NADP(H) is an important cofactor that controls many fundamental cellular processes. We have determined the crystal structure of HSCARG, a novel NADPH sensor, and found that it forms an asymmetrical dimer with only one subunit occupied by an NADPH molecule, and the two subunits have dramatically different conformations. To study the role of NADPH in...
A novel human Glyco_18 domain-containing protein, SI-CLP, was detected recently in human bronchoalveolar lavage of patients with chronic inflammatory disorders of the respiratory tract and peripheral-blood leukocytes. The expression of SI-CLP is up-regulated by dexamethasone or IL-4 and involved in the Th2 cell pathway. To further investigate its s...
The nucleocapsid protein (N) of vesicular stomatitis virus and other rhabdoviruses plays a central role in the assembly and template functions of the viral N-RNA complex. The crystal structure of the viral N-RNA complex suggests that the central region of the N protein interacts with the viral RNA. Sequence alignment of rhabdovirus N proteins revea...
The nucleocapsid protein (NP) of mumps virus (MuV), a paramyxovirus, was coexpressed with the phosphoprotein (P) in Escherichia coli. The NP and P proteins form a soluble complex containing RNA. Under a transmission electron microscope, the NP-RNA complex
appears as a nucleocapsidlike ring that has a diameter of approximately 20 nm with 13 subunits...
Surface antigen preS of Hepatitis B virus plays fundamental roles in mediating receptor recognition and virus internalization. Myristoylation at N-terminal Gly(2) residue of preS is essential for viral attachment and infectivity. A number of myristoylated proteins have been shown to undergo a conformational change (myristoyl switch) that alters the...
PDHK2 is a mitochondrial protein kinase that phosphorylates pyruvate dehydrogenase complex, thereby down-regulating the oxidation
of pyruvate. Here, we present the crystal structure of PDHK2 bound to the inner lipoyl-bearing domain of dihydrolipoamide
transacetylase (L2) determined with or without bound adenylyl imidodiphosphate. Both structures re...
NADPH is an important cofactor in many biosynthesis pathways that control fundamental cellular processes. We recently determined the crystal structure of HSCARG, with functions previously unknown, and demonstrated it is an NADPH sensor, which undergoes restructuring and redistribution in response to changes of intracellular NADPH/NADP levels. In th...
As a hepatitis B virus (HBV) envelope domain, preS plays significant roles in receptor recognition and viral infection. However, the regions critical for maintaining a stable and functional conformation of preS are still unclear and require further investigation. In order to unravel these regions, serially truncated fragments of preS were construct...
The objective of structural proteomics is to determine the structures of all protein folds found in nature and develop a public resource to organize and analyze protein structures and fold families. High throughput (HTP) methods, which can process multiple samples in parallel, saving both time and cost, play important roles in achieving this goal....
The emergence of drug resistant viruses, together with the possibility of increased virulence, is an important concern in the development of new antiviral compounds. Cidofovir (CDV) is a phosphonate nucleotide that is approved for use against cytomegalovirus retinitis and for the emergency treatment of smallpox or complications following vaccinatio...
The crystal structure of the vesicular stomatitis virus nucleoprotein (N) in complex with RNA reveals extensive and specific
intermolecular interactions among the N molecules in the 10-member oligomer. What roles these interactions play in encapsidating
RNA was studied by mutagenesis of the N protein. Three N mutants intended for disruption of the...
Rhabdovirus is a negative strand RNA virus that packages a ribonucleoprotein (RNP) complex. The RNP is composed of a genome that is encapsidated completely by the nucleoprotein (N). Structural comparisons of the RNA-nucleoprotein complexes from two members, vesicular stomatitis virus (VSV) and rabies virus (RABV), revealed highly conserved characte...
Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a potential target for structure-based inhibitor design for the treatment of parasitic diseases. We created point mutants of Thermoanaerobacter tengcongensis HGPRT and tested their activities to identify side chains that were important for function. Mutating residues Leu160 and Lys133 substa...
NAD(P) has long been known as an essential energy-carrying molecule in cells. Recent data, however, indicate that NAD(P) also plays critical signaling roles in regulating cellular functions. The crystal structure of a human protein, HSCARG, with functions previously unknown, has been determined to 2.4-Å resolution. The structure reveals that HSCARG...
Structures of the nucleoprotein of three negative strand RNA virus families, borna disease virus, rhabdovirus and influenza A virus, are now available. Structural comparisons showed that the topology of the RNA binding region from the three proteins is very similar. The RNA was shown to fit into a cavity formed by the two distinct domains of the RN...
Expression of higher eukaryotic genes as soluble, stable recombinant proteins is still a bottleneck step in biochemical and structural studies of novel proteins today. Correct identification of stable domains/fragments within the open reading frame (ORF), combined with proper cloning strategies, can greatly enhance the success rate when higher euka...
Hepatitis B virus (HBV) infection is a serious health problem worldwide. Treatment recommendation and response are mainly indicated by viral load, e antigen (HBeAg) seroconversion, and ALT levels. The S antigen (HBsAg) seroconversion is much less frequent. Since HBeAg can be negative in the presence of high viral replication, preS antigen (HBpreSAg...
The antiviral activity of a new series of thymidine analogs was determined against vaccinia virus (VV), cowpox virus (CV), herpes simplex virus, and varicella-zoster virus. Several compounds were identified that had good activity against each of the viruses, including a set of novel 5-substituted deoxyuridine analogs. To investigate the possibility...
Did drug researchers have a lucky break when they developed antiviral drugs for influenza? Crystal structures of enzymes from the H5N1 virus suggest that they did, and provide avenues for further exploration. H5N1 avian flu virus is so named from the haemagglutinin (H) and neuraminidase (N) proteins on the virus coat; each protein comes in several...
Vesicular stomatitis virus is a negative-stranded RNA virus. Its nucleoprotein (N) binds the viral genomic RNA and is involved
in multiple functions including transcription, replication, and assembly. We have determined a 2.9 angstrom structure of a
complex containing 10 molecules of the N protein and 90 bases of RNA. The RNA is tightly sequestered...
Vesicular stomatitis virus (VSV) is a non-segmented negative-stranded RNA virus. The nucleocapsid (N) protein of VSV is found tightly associated with the viral genomic RNA and this complex serves as the template for transcription and replication. A method for the soluble expression of the N protein in Escherichia coli has previously been reported....
Bunyamwera virus (BUNV) is the prototypic member of the Bunyaviridae family of segmented negative-sense RNA viruses. The BUNV nucleocapsid protein has been cloned and expressed in Escherichia coli. The purified protein has been crystallized and a complete data set has been collected to 3.3 angstroms resolution at a synchrotron source. Crystals of t...
CARP is a novel pro-apoptotic protein that has been cloned and characterized in our previous report. Previous studies showed that suppression of CARP expression results in cell proliferation in several mammalian cell lines and over-expression of CARP leads to apoptosis and inhibition of proliferation in seven tumor cell lines [Liu et al., CARP is a...
Citations
... The software has been used to analyze around 1151 protein structures obtained through Nuclear Magnetic Resonance (NMR) technology, aiding in the capture of dynamic residue contacts. It was specifically employed for key residue capture in NMR PDB files (e.g., 1MEK) [9], molecular dynamic simulation capture of the BRD4 protein (four states) [10], ligand binding capture of CYP17A1 structures with drugs [11], and DNA binding interactions of the SPI1 protein-DNA complex structures [12]. In summary, ARIP is a comprehensive and user-friendly software tool that supports the analysis of nucleic acids and other molecules stored in PDB format. ...
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... The model relies only on mass action reactions, meaning the only factors considered when calculating the reaction rate are the reactant concentrations, and incorporates the synthesis, degradation, and assembly reactions of VSV and can easily be simulated with the standard Gillespie stochastic simulation algorithms. The model also incorporates a transition of the viral genomes from an active to an inactive state facilitated by the M protein [1,2,18]. The model is the most accurate to date for predicting changes in mean virion production in gene shuffled VSV variants [19] and can additionally capture the distribution of the number of viruses produced by VSV. ...
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... PCR with PGMY primers was used for HPV genotyping, followed by reverse line blot hybridization, 23 which detects 31 HPV genotypes including HPV 6,11,16,18,26,31,33,34,35,39,40,42,44,45,51,52,53,54,55,56,57,58,59,66,68,69,70,73,82,83, and 84. ...
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... Above results showed that eEF1A inhibited the transcription and replication of SCRV genomes but did not directly degrade N protein, which suggests that eEF1A might inhibit the function of N protein during SCRV infection. Previous research has found that the N protein is involved in the transcription and replication of the rhabdovirus genome by forming a complex with the P protein (17). And the N protein itself also forms oligomers consisting of 2-10 monomers when it encases the viral genome (47). ...
... VSV продемонстрировал противоопухолевую активность в широком спектре раковых клеток, включая остеосаркому [12], рак шейки матки [13], РМЖ [14], меланому [15], гепатоцеллюлярную карциному (ГЦК) [16], рак поджелудочной железы [17] и глиобластому [4,18]. ...
... In addition to viral DNA/RNA, viral proteins can also serve as targets for PRRs 18 . Among these viral proteins, the nucleocapsid protein (N protein or NP) has a crucial role by binding to viral RNAs and safeguarding them against nucleases [19][20][21] . To explore the interaction between NP and host proteins, we transfected a vector encoding the NP of vesicular stomatitis virus (VSV-NP) into HEK293T cells. ...
... J. Hodge та співавт. [74] показали, що введення імунних ДК із надлишковою експресією miR-155 тваринам із раком молочної залози приводило до посилення протипухлинного імунітету за рахунок збільшення продукції ефекторних Т-клітин у лімфогемопоетичних органах, що обумовлювало пригнічення росту пухлини та різке зменшення кількості й розмірів метастатичних вогнищ у легенях. ...
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... The highly expressed ILP-2 in the cytoplasm will produce a large amount of antiapoptotic information, resulting in changes in the conformation of mitochondrial membrane molecules, and a large amount of ILP-2 specifically binds to Smac, so that Smac cannot release the blocking effect of caspase-IAP, thereby antagonizing Smac proapoptotic effect (79). Moreover, ILP-2 can also reduce the relative amount of free Smac in the cytoplasm by activating the ubiquitination pathway, and the low level of Smac in the cytoplasm cannot express its caspase protein kinase activity to activate related caspases, which leads to the inhibition of apoptotic signal generation and thus inhibits apoptosis (80,81). In addition, ILP-2 is able to further bind activated caspases, which in turn inhibits the activity of caspases, thus achieving inhibition of apoptosis. ...
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... Gene expression may evolve, and this is a major source of trait/phenotype diversity [231]. The dynamics driving the growth and evolution of genomes is the Fibonacci "golden ratio" that describes predictable patterns that occur in all dynamic systems, and it is an indicator of balance [232]. This ratio has also been found in the human genome within the frequencies of different nucleotides (the basic building block of nucleic acids-the primary information-carrying RNA or DNA molecules that make up genetic material). ...
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... reconstructions of full-length, membrane-bound prefusion HCMV gB (28)(29)(30) revealed a shorter and more 50 compact structure than observed for postfusion gB and suggested a domain architecture similar to 51 prefusion G from vesicular stomatitis virus (VSV) (31). Recently, a 3.6 Å resolution cryo-electron 52 microscopy (cryo-EM) structure of prefusion HCMV gB was determined using detergent-solubilized full-53 length gB purified from virions, complexed with the neutralizing human antibody SM5-1 (32), and 54 stabilized in the prefusion conformation with a thiourea fusion inhibitor and a chemical cross-linker (23). ...
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