Liwen Niu

University of Science and Technology of China, Luchow, Anhui Sheng, China

Are you Liwen Niu?

Claim your profile

Publications (114)337.27 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Faithful segregation of chromosomes in mammalian cells requires bi-orientation of sister chromatids, which relies on the sensing of correct attachments between spindle microtubules and kinetochores. Although the mechanisms underlying cyclin-dependent kinase 1 (CDK1) activation, which triggers mitotic entry, have been extensively studied, the regulatory mechanisms that couple CDK1-cyclin B activity to chromosome stability are not well understood. Here, we identified a signaling axis in which Aurora B activity is modulated by CDK1-cyclin B via the acetyltransferase TIP60 in human cell division. CDK1-cyclin B phosphorylates Ser90 of TIP60, which elicits TIP60-dependent acetylation of Aurora B and promotes accurate chromosome segregation in mitosis. Mechanistically, TIP60 acetylation of Aurora B at Lys215 protects Aurora B's activation loop from dephosphorylation by the phosphatase PP2A to ensure a robust, error-free metaphase-anaphase transition. These findings delineate a conserved signaling cascade that integrates protein phosphorylation and acetylation with cell cycle progression for maintenance of genomic stability.
    No preview · Article · Feb 2016 · Nature Chemical Biology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: SSRP1 is a subunit of the FACT complex, an important histone chaperone required for transcriptional regulation, DNA replication and damage repair. SSRP1 also plays important roles in transcriptional regulation independent of Spt16 and interacts with other proteins. Here, we report the crystal structure of the middle domain of SSRP1. It consists of tandem pleckstrin homology (PH) domains. These domains differ from the typical PH domain in that PH1 domain has an extra conserved βαβ topology. SSRP1 contains the well-characterized DNA-binding HMG-1 domain. Our studies revealed that SSRP1-M can also participate in DNA binding, and that this binding involves one positively charged patch on the surface of the structure. In addition, SSRP1-M did not bind to histones, which was assessed through pull-down assays. This aspect makes the protein different from other related proteins adopting the double PH domain structure. Our studies facilitate the understanding of SSRP1 and provide insights into the molecular mechanisms of interaction with DNA and histones of the FACT complex.
    Full-text · Article · Dec 2015 · Scientific Reports
  • Source
    Fan Zhang · Yang Song · Liwen Niu · Maikun Teng · Xu Li
    [Show abstract] [Hide abstract]
    ABSTRACT: Peptidyl-tRNA hydrolase (Pth) catalyzes the release of tRNA to relieve peptidyl-tRNA accumulation. Because Pth activity is essential for the viability of bacteria, Pth is regarded as a promising target for the discovery of new antimicrobial agents. Here, the structure of Pth from the Gram-positive bacterium Staphylococcus aureus (SaPth) was solved by X-ray crystallography at a 2.25 Å resolution. The SaPth structure exhibits significant structural similarity with other members of the Pth superfamily, with a conserved α/β/α sandwich fold. A molecular phylogenetic analysis and a structure database search indicated that SaPth is most similar to its homolog in Streptococcus pyogenes, but it has a different substrate-binding cleft state.
    Full-text · Article · Oct 2015 · Acta Biochimica et Biophysica Sinica
  • [Show abstract] [Hide abstract]
    ABSTRACT: Spt5 (NusG in bacteria) is the only RNA polymerase-associated factor known to be conserved in all three domains of life. In archaea and eukaryotes, Spt5 associates with Spt4, an elongation factor that is absent in bacteria, to form a functional heterodimeric complex. Previous studies suggest that the Spt4:Spt5 complex interacts directly with DNA at the double-stranded DNA exit tunnel of RNA polymerase to regulate gene transcription. In this study, the DNA-binding ability of Spt4:Spt5 from the archaeon Methanocaldococcus jannaschii was confirmed via nuclear magnetic resonance chemical shift perturbation and fluorescence polarization assays. Crystallographic analysis of the full-length MjSpt4:Spt5 revealed two distinct conformations of the C-terminal KOW domain of Spt5. A similar alkaline region was found on the Spt4:Spt5 surface in both crystal forms, and identified as double-stranded DNA binding patch through mutagenesis-fluorescence polarization assays. Based on these structural and biochemical data, the Spt4:Spt5-DNA binding model was built for the first time.
    No preview · Article · Oct 2015 · Journal of Structural Biology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Lpg0406, a hypothetical protein from Legionella pneumophila, belongs to carboxymuconolactone decarboxylase (CMD) family. We determined the crystal structure of lpg0406 both in its apo and reduced form. The structures reveal that lpg0406 forms a hexamer and have disulfide exchange properties. The protein has an all-helical fold with a conserved thioredoxin-like active site CXXC motif and a proton relay system similar to that of alkylhydroperoxidase from Mycobacterium tuberculosis (MtAhpD), suggesting that lpg0406 might function as an enzyme with peroxidase activity and involved in antioxidant defense. A comparison of the size and the surface topology of the putative substrate-binding region between lpg0406 and MtAhpD indicates that the two enzymes accommodate the different substrate preferences. The structural findings will enhance understanding of the CMD family protein structure and its various functions. This article is protected by copyright. All rights reserved.
    No preview · Article · Sep 2015 · Protein Science
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: UbiG and Coq3 (orthologue in eukaryotes) are SAM-MTases (S-adenosylmethionine-dependent methyltransferases) that catalyse both O-methylation steps in CoQ biosynthesis from prokaryotes to eukaryotes. However, the detailed molecular mechanism by which they function remains elusive. In the present paper, we report that UbiG/Coq3 defines a novel class of membrane-binding proteins. Escherichia coli UbiG binds specifically to liposomes containing PG (phosphatidylglycerol) or CL (cardiolipin, or diphosphatidylglycerol), two major lipid components of the E. coli plasma membrane, whereas human and yeast Coq3 display a strong preference for liposomes enriched with CL, a signature lipid of the mitochondrial membrane. The crystal structure of UbiG from E. coli was determined at 2.1 Å (1 Å=0.1 nm) resolution. The structure exhibits a typical Class I SAM-MTase fold with several variations, including a unique insertion between strand β5 and helix α10. This insertion is highly conserved and is required for membrane binding. Mutation of the key residues renders UbiG unable to efficiently bind liposome in vitro and the mutant fails to rescue the phenotype of ΔubiG strain in vivo. Taken together, our results shed light on a novel biochemical function of the UbiG/Coq3 protein.
    Full-text · Article · Aug 2015 · Biochemical Journal
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The SaeR/S two-component regulatory system is essential for controlling the expression of many virulence factors in Staphylococcus aureus . SaeR, a member of the OmpR/PhoB family, is a response regulator with an N-terminal regulatory domain and a C-terminal DNA-binding domain. In order to elucidate how SaeR binds to the promoter regions of target genes, the crystal structure of the DNA-binding domain of SaeR (SaeR DBD ) was solved at 2.5 Å resolution. The structure reveals that SaeR DBD exists as a monomer and has the canonical winged helix–turn–helix module. EMSA experiments suggested that full-length SaeR can bind to the P1 promoter and that the binding affinity is higher than that of its C-terminal DNA-binding domain. Five key residues on the winged helix–turn–helix module were verified to be important for binding to the P1 promoter in vitro and for the physiological function of SaeR in vivo .
    Full-text · Article · Aug 2015 · Acta Crystallographica Section D Biological Crystallography
  • Source
    Hui Lv · Yuwei Zhu · Yu Qiu · Liwen Niu · Maikun Teng · Xu Li
    [Show abstract] [Hide abstract]
    ABSTRACT: After deadenylation and decapping, cytoplasmic mRNA can be digested in two opposite directions: in the 5'-3' direction by Xrn1 or in the 3'-5' direction by the exosome complex. Recently, a novel 3'-5' RNA-decay pathway involving Dis3l2 has been described that differs from degradation by Xrn1 and the exosome. The product of the Schizosaccharomyces pombe gene SPAC2C4.07c was identified as a homologue of human Dis3l2. In this work, the 2.8 Å resolution X-ray crystal structure of S. pombe Dis3l2 (SpDis3l2) is reported, the conformation of which is obviously different from that in the homologous mouse Dis3l2-RNA complex. Fluorescence polarization assay experiments showed that RNB and S1 are the primary RNA-binding domains and that the CSDs (CSD1 and CSD2) play an indispensable role in the RNA-binding process of SpDis3l2. Taking the structure comparison and mutagenic experiments together, it can be inferred that the RNA-recognition pattern of SpDis3l2 resembles that of its mouse homologue rather than that of the Escherichia coli RNase II-RNA complex. Furthermore, a drastic conformation change could occur following the binding of the RNA substrate to SpDis3l2.
    Full-text · Article · Jun 2015 · Acta Crystallographica Section D Biological Crystallography
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Human PRS1, which is indispensable for the biosynthesis of nucleotides, deoxynucleotides and their derivatives, is associated directly with multiple human diseases because of single base mutation. However, a molecular understanding of the effect of these mutations is hampered by the lack of understanding of its catalytic mechanism. Here, we reconstruct the 3D EM structure of the PRS1 apo state. Together with the native stain EM structures of AMPNPP, AMPNPP and R5P, ADP and the apo states with distinct conformations, we suggest the hexamer is the enzymatically active form. Based on crystal structures, sequence analysis, mutagenesis, enzyme kinetics assays, and MD simulations, we reveal the conserved substrates binding motifs and make further analysis of all pathogenic mutants.
    Full-text · Article · Mar 2015 · PLoS ONE
  • Wei He · Zhi Liang · Maikun Teng · Liwen Niu
    [Show abstract] [Hide abstract]
    ABSTRACT: A large number of proteins contain metal ions that are essential for their stability and biological activity. Identifying and characterizing metal-binding sites through computational methods is necessary when experimental clues are lacking. Almost all published computational methods are designed to distinguish metal-binding sites from non-metal-binding sites. However, discrimination between different types of metal-binding sites is also needed to make more accurate predictions. In the present work, we proposed a novel algorithm called mFASD, which could discriminate different types of metal-binding sites effectively based on 3D structure data and is useful for accurate metal-binding site prediction. mFASD captures the characteristics of a metal-binding site by investigating the local chemical environment of a set of functional atoms that are considered to be in contact with the bound metal. Then a distance measure defined on functional atom sets enables the comparison between different metal-binding sites. The algorithm could discriminate most types of metal-binding sites from each other with high sensitivity and accuracy. We showed that cascading our method with existing ones could achieve a substantial improvement of the accuracy for metal-binding site prediction. Availability: Source code and data used are freely available from http://staff.ustc.edu.cn/~liangzhi/mfasd/. liangzhi@ustc.edu.cn, hwkobe@mail.ustc.edu.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. © The Author (2015). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    No preview · Article · Feb 2015 · Bioinformatics
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dephospho-CoA kinase (DPCK; EC 2.7.1.24) catalyzes the final step in the coenzyme A biosynthetic pathway. DPCK transfers a phosphate group from ATP to the 3-hydroxyl group of the ribose of dephosphocoenzyme A (dCoA) to yield CoA and ADP. Upon the binding of ligands, large conformational changes is induced in DPCKs, as well as in many other kinases, to shield the bound ATP in their catalytic site from the futile hydrolysis by bulk water molecules To investigate the molecular mechanisms underlying the phosphoryl transfer during DPCK catalytic cycle, we determined the crystal structures of the L. pneumophila DPCK (LpDPCK) both in its apo-form and in complex with ATP. The structures reveal that LpDPCK comprises of three domains, the classical core domain, the CoA domain, and the LID domain, which are packed together to create a central cavity for substrate-binding and enzymatic catalysis. The binding of ATP induces large conformational changes, including a hingebending motion of the CoA binding domain and the “helix to loop” conformational change of the P-loop. Finally, modeling of a dCoA molecule to the enzyme provides insights into the catalytic mechanism of DPCK.
    No preview · Article · Oct 2014 · Journal of Structural Biology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The short palate, lung and nasal epithelial clone 1 (SPLUNC1) protein is a member of the palate, lung, and nasal epithelium clone (PLUNC) family, also known as bactericidal/permeability-increasing (BPI) fold-containing protein, family A, member 1 (BPIFA1). SPLUNC1 is an abundant protein in human airways, but its function remains poorly understood. The lipid ligands of SPLUNC1 as well as other PLUNC family members are largely unknown, although some reports provide evidence that lipopolysaccharide (LPS) could be a lipid ligand. Unlike previous hypotheses, we found significant structural differences between SPLUNC1 and BPI. Recombinant SPLUNC1 produced in HEK 293 cells harbored several molecular species of sphingomyelin and phosphatidylcholine as its ligands. Significantly, in vitro lipid-binding studies failed to demonstrate interactions between SPLUNC1 and LPS, lipoteichoic acid, or polymyxin B. Instead, one of the major and most important pulmonary surfactant phospholipids, dipalmitoylphosphatidylcholine (DPPC), bound to SPLUNC1 with high affinity and specificity. We found that SPLUNC1 could be the first protein receptor for DPPC. These discoveries provide insight into the specific determinants governing the interaction between SPLUNC1 and lipids and also shed light on novel functions that SPLUNC1 and other PLUNC family members perform in host defense.-Ning, F., Wang, C., Berry, K. Z., Kandasamy, P., Liu, H., Murphy, R. C., Voelker, D. R., Nho, C. W., Pan, C.-H., Dai, S., Niu, L., Chu, H-W., Zhang, G. Structural characterization of the pulmonary innate immune protein SPLUNC1 and identification of lipid ligands.
    Full-text · Article · Sep 2014 · The FASEB Journal
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Staphylococcus aureus is a highly versatile pathogen that can infect human tissue by producing a large arsenal of virulence factors that are tightly regulated by a complex regulatory network. Rot, which shares sequence similarity with SarA homologues, is a global regulator that regulates numerous virulence genes. However, the recognition model of Rot for the promoter region of target genes and the putative regulation mechanism remain elusive. In this study, the 1.77 Å resolution X-ray crystal structure of Rot is reported. The structure reveals that two Rot molecules form a compact homodimer, each of which contains a typical helix–turn–helix module and a β-hairpin motif connected by a flexible loop. Fluorescence polarization results indicate that Rot preferentially recognizes AT-rich dsDNA with ∼30-base-pair nucleotides and that the conserved positively charged residues on the winged-helix motif are vital for binding to the AT-rich dsDNA. It is proposed that the DNA-recognition model of Rot may be similar to that of SarA, SarR and SarS, in which the helix–turn–helix motifs of each monomer interact with the major grooves of target dsDNA and the winged motifs contact the minor grooves. Interestingly, the structure shows that Rot adopts a novel dimerization model that differs from that of other SarA homologues. As expected, perturbation of the dimer interface abolishes the dsDNA-binding ability of Rot, suggesting that Rot functions as a dimer. In addition, the results have been further confirmed in vivo by measuring the transcriptional regulation of α-toxin, a major virulence factor produced by most S. aureus strains.
    Full-text · Article · Sep 2014 · Acta Crystallographica Section D Biological Crystallography
  • Source

    Full-text · Dataset · Aug 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: DnaT is a primosomal protein that is required for the stalled replication fork restart in Escherichia coli. As an adapter, DnaT mediates the PriA-PriB-ssDNA ternary complex and the DnaB/C complex. However, the fundamental function of DnaT during PriA-dependent primosome assembly is still a black box. Here, we report the 2.83 Å DnaT84–153-dT10 ssDNA complex structure, which reveals a novel three-helix bundle single-stranded DNA binding mode. Based on binding assays and negative-staining electron microscopy results, we found that DnaT can bind to phiX 174 ssDNA to form nucleoprotein filaments for the first time, which indicates that DnaT might function as a scaffold protein during the PriA-dependent primosome assembly. In combination with biochemical analysis, we propose a cooperative mechanism for the binding of DnaT to ssDNA and a possible model for the assembly of PriA-PriB-ssDNA-DnaT complex that sheds light on the function of DnaT during the primosome assembly and stalled replication fork restart. This report presents the first structure of the DnaT C-terminal complex with ssDNA and a novel model that explains the interactions between the three-helix bundle and ssDNA.
    Full-text · Article · Jul 2014 · Nucleic Acids Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: Yeast Hif1, a homologue of human nuclear autoantigenic sperm protein (NASP), is a histone chaperone that involved in various protein complexes modifying histones during telomeric silencing and chromatin reassembly. For elucidating the structural basis of Hif1, here, we present crystal structure of Hif1 that consists of a superhelixed TPR domain and an extended acid loop covering the rear of TPR domain, which represents typical characters of SHNi-TPR (Sim3-Hif1-NASP interrupted TPR) proteins. Our binding assay indicates that Hif1 could bind to histone octamer via histone H3 and H4. However, the acid loop is crucial for the binding of histones while it may also change the conformation of TPR groove. By binding to core histone complex Hif1 may recruit functional protein complexes to modify histones during chromatin reassembly.
    No preview · Article · Jun 2014 · Biochemical Journal
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Arginine methylation plays vital roles in the cellular functions of the protozoan Trypanosoma brucei. The T. brucei arginine methyltransferase 6 (TbPRMT6) is a type I arginine methyltransferase homologous to human PRMT6. In this study, we report the crystal structures of apo-TbPRMT6 and its complex with the reaction product S-adenosyl-homocysteine (SAH). The structure of apo-TbPRMT6 displays several features that are different from those of type I PRMTs that were structurally characterized previously, including four stretches of insertion, the absence of strand β15, and a distinct dimerization arm. The comparison of the apo-TbPRMT6 and SAH-TbPRMT6 structures revealed the fine rearrangements in the active site upon SAH binding. The isothermal titration calorimetry results demonstrated that SAH binding greatly increases the affinity of TbPRMT6 to a substrate peptide derived from bovine histone H4. The western blotting and mass spectrometry results revealed that TbPRMT6 methylates bovine histone H4 tail at arginine 3 but cannot methylate several T. brucei histone tails. In summary, our results highlight the structural differences between TbPRMT6 and other type I PRMTs and reveal that the active site rearrangement upon SAH binding is important for the substrate binding of TbPRMT6.
    Full-text · Article · Feb 2014 · PLoS ONE
  • Xiao Wang · Ye Yuan · Maikun Teng · Liwen Niu · Yongxiang Gao
    [Show abstract] [Hide abstract]
    ABSTRACT: Adenylate kinase plays a very important role in regulating adenylate species in the cell. Methanocaldococcus jannaschii is a rich resource of unique enzymes. Here, MJ0458, an adenylate kinase from M. jannaschii, was crystallized. A set of X-ray diffraction data to 2.70 Å resolution was collected on beamline BL-17U of the Shanghai Synchrotron Radiation Facility (SSRF). The crystal belonged to space group P41212 or P43212. The unit-cell parameters were a = b = 76.18, c = 238.70 Å, α = β = γ = 90°.
    No preview · Article · Nov 2013 · Acta Crystallographica Section F Structural Biology and Crystallization Communications
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Heterogeneous nuclear ribonucleoprotein L (hnRNP L) is an abundant RNA-binding protein implicated in many bioprocesses including pre-mRNA processing, mRNA export of intronless genes, internal ribosomal entry site (IRES)-mediated translation, and chromatin modification. It contains four RNA recognition motifs (RRMs) that bind with CA repeats or CA-rich elements. In this study, surface plasmon resonance (SPR) spectroscopy assays revealed that all four RRM domains contribute to RNA-binding. Furthermore, we elucidated the crystal structures of hnRNP L RRM1 and RRM34 at 2.0 Å and 1.8 Å, respectively. These RRMs all adopt the typical β1α1β2β3α2β4 topology, except for an unusual fifth β-strand in RRM3. RRM3 and RRM4 interact intimately with each other mainly through helical surfaces, leading the two β-sheets to face opposite directions. Structure-based mutations and SPR assay results suggested that the β-sheets of RRM1 and RRM34 are accessible for RNA binding. FRET-based gel shift assays (FRET-EMSA) and steady-state FRET assays (ss-FRET), together with cross-linking and dynamic light scattering (DLS) assays, demonstrated that hnRNP L RRM34 facilitates RNA looping when binding to two appropriately separated binding sites within the same target pre-mRNA. EMSA and ITC binding studies with in vivo target RNA suggested that hnRNP L-mediated RNA looping may occur in vivo. Our study provides a mechanistic explanation for the dual functions of hnRNP L in alternative-splicing regulation as an activator or repressor.
    Full-text · Article · Aug 2013 · Journal of Biological Chemistry
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Nit (nitrilase-like) protein subfamily constitutes branch 10 of the nitrilase superfamily. Nit proteins are widely distributed in nature. Mammals possess two members of the Nit subfamily, namely Nit1 and Nit2. Based on sequence similarity, yeast Nit2 (yNit2) is a homologue of mouse Nit1, a tumour-suppressor protein whose substrate specificity is not yet known. Previous studies have shown that mammalian Nit2 (also a putative tumour suppressor) is identical to ω-amidase, an enzyme that catalyzes the hydrolysis of α-ketoglutaramate (α-KGM) and α-ketosuccinamate (α-KSM) to α-ketoglutarate (α-KG) and oxaloacetate (OA), respectively. In the present study, crystal structures of wild-type (WT) yNit2 and of WT yNit2 in complex with α-KG and with OA were determined. In addition, the crystal structure of the C169S mutant of yNit2 (yNit2-C169S) in complex with an endogenous molecule of unknown structure was also solved. Analysis of the structures revealed that α-KG and OA are covalently bound to Cys169 by the formation of a thioester bond between the sulfhydryl group of the cysteine residue and the γ-carboxyl group of α-KG or the β-carboxyl group of OA, reflecting the presumed reaction intermediates. However, an enzymatic assay suggests that α-KGM is a relatively poor substrate of yNit2. Finally, a ligand was found in the active site of yNit2-C169S that may be a natural substrate of yNit2 or an endogenous regulator of enzyme activity. These crystallographic analyses provide information on the mode of substrate/ligand binding at the active site of yNit2 and insights into the catalytic mechanism. These findings suggest that yNit2 may have broad biological roles in yeast, especially in regard to nitrogen homeostasis, and provide a framework for the elucidation of the substrate specificity and biological role of mammalian Nit1.
    No preview · Article · Aug 2013 · Acta Crystallographica Section D Biological Crystallography

Publication Stats

1k Citations
337.27 Total Impact Points

Institutions

  • 1997-2015
    • University of Science and Technology of China
      • • School of Life Sciences
      • • Hefei National Laboratory for Physical Sciences at the Microscale
      • • Department of Molecular Biology and Cell Biology
      Luchow, Anhui Sheng, China
  • 2013
    • Anhui University
      Luchow, Anhui Sheng, China
  • 2001-2013
    • Chinese Academy of Sciences
      • Molecular Biology and Cell Biology Laboratory
      Peping, Beijing, China
  • 2005-2011
    • Hefei Institute of Physical Sciences, Chinese Academy of Sciences
      Luchow, Anhui Sheng, China
  • 2005-2007
    • Cornell University
      Ithaca, New York, United States