Preprint
To read the file of this research, you can request a copy directly from the authors.

Abstract

Currently, the world is struggling with the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Prion-like domains are critical for virulence and the development of therapeutic targets; however, the prion-like domains in the SARS-CoV-2 proteome have not been analyzed. In this in silico study, using the PLAAC algorithm, we identified the presence of prion-like domains in SARS-CoV-2 spike protein. Compared with other viruses, a striking difference was observed in the distribution of prion-like domains in the spike, since SARS-CoV-2 was the only coronavirus with a prion-like domain found in the receptor-binding domain of the S1 region of the spike protein. The presence and unique distribution of prion-like domains in the SARS-CoV-2 receptor-binding domains of spike proteins is particularly interesting, since although SARS-CoV-2 and SARS-CoV S share the same host cell receptor, angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 demonstrates a 10- to 20-fold higher affinity for ACE2. Finally, we identified prion-like domains in the α1 helix of the ACE2 receptor that interacts with the viral receptor-binding domain of SARS-CoV-2. Taken together, the present findings indicate that the identified PrDs in the SARS-CoV-2 receptor-binding domain (RBD) and ACE2 region that interacts with RBD have important functional roles in viral adhesion and entry.

No file available

Request Full-text Paper PDF

To read the file of this research,
you can request a copy directly from the authors.

... The spike protein binds to receptors on human cells. Although SARS-CoV and SARS-CoV-2 both bind to angiotensin-converting enzyme-2 (ACE-2), SARS-CoV-2 binds at 10 to 20 times higher affinity (Tetz and Tetz 2020).SARS-CoV-2 has been reported to be the only coronavirus with such a unique distribution of PrDs in its spike protein, which occur at the receptor-binding domain at S1 region. Therefore, it has been suggested that the PrDs identified in SARS-CoV-2 receptor-binding domain may have an important role in its function during adhesion and entry of SARS-CoV-2 to the host cell (Tetz and Tetz 2020). ...
... Although SARS-CoV and SARS-CoV-2 both bind to angiotensin-converting enzyme-2 (ACE-2), SARS-CoV-2 binds at 10 to 20 times higher affinity (Tetz and Tetz 2020).SARS-CoV-2 has been reported to be the only coronavirus with such a unique distribution of PrDs in its spike protein, which occur at the receptor-binding domain at S1 region. Therefore, it has been suggested that the PrDs identified in SARS-CoV-2 receptor-binding domain may have an important role in its function during adhesion and entry of SARS-CoV-2 to the host cell (Tetz and Tetz 2020). ...
... Interestingly during the recent COVID-19 pandemic, PrDs have been discovered in proteins of SARS-CoV-2 (Tetz and Tetz 2020). As viral proteins are a major player in viral persistence (Roeth et al. 2004;Mankouri et al. 2009;Rossi and Colin 2015;Kane and Golovkina 2010), we suggest that the discovery of PrDs among viral proteins implicates these in evolution among viruses. ...
Article
Full-text available
Self-replicating proteins or prions deviate from the central dogma of replication. The discovery of prion-like domains in coronavirus SARS-CoV-2 suggests their possible role in viral evolution. Here, we have outlined the possible role of selfreplicating protein-like domains in the emergence of novel viruses. Further studies are needed to understand the function of these viral self-replicating protein-like domains and whether they could be antiviral target(s) for the development of effective antiviral agents in the future.
... The longest Fibonacci structures would therefore measure 2584 bases. When looking for such structures, the first one found is at location 1200: therefore, covering the bases situated between 1201 and 3784 (1200 + 2584 Three other sequences were obtained with BLAST using a selection area of the 114 nucleotides PRION region Tetz and Tetz (2020) with their 8 amino acids mutations in OMICRON; see https://covariants.org/variants/21K.Omicron The PRION region described in the work of Tetz and Tetz (2020) are located between amino acids 473-510 of the Spike protein. ...
... The longest Fibonacci structures would therefore measure 2584 bases. When looking for such structures, the first one found is at location 1200: therefore, covering the bases situated between 1201 and 3784 (1200 + 2584 Three other sequences were obtained with BLAST using a selection area of the 114 nucleotides PRION region Tetz and Tetz (2020) with their 8 amino acids mutations in OMICRON; see https://covariants.org/variants/21K.Omicron The PRION region described in the work of Tetz and Tetz (2020) are located between amino acids 473-510 of the Spike protein. ...
... What does that mean? In fact, the prion-region of the spike plays an essential role in cell adhesion and entry and therefore possibly as well in the bloodbrain barrier crossing Tetz and Tetz (2020), Buzhdygan (2020), Reynolds (2021) [Tetz, Buzhdygan, Reynolds]. This concentration of mutation confirms this gene region is a key element in the infectiousness of the virus and that the virus is subjected to a strong adaptation pressure. ...
Article
Full-text available
We analyzed 15 genomes and Spikes of the new OMICRON variant, on the one hand 7 from the very first 21K lineage (South Africa, USA, Belgium, Canada), on the other hand 8 from the later second sister-clade 21L (USA , Switzerland, UK). We applied, at the scale of the whole genome and the spike gene, the biomathematics method of Fibonacci meta-structure fractal analysis applied to the UA / CG proportions. There appears a total rupture of this variant with respect to all the previous variants, and a strong differentiation between these 2 OMICRON lines. We have evidenced the RUPTURE of OMICRON with respect to ALL the previous variants: D614G, ALPHA, BETA, GAMMA, DELTA. In particular, we suggest that the mRNA stabilizing secondary structure ("hairpin" conformation) in the spike of all variants is degraded in OMICRON, probably making its mRNA more fragile. The loss of long-range fractal meta-structures in the OMICRON spike gene are in line with common knowledge on the mechanisms of epidemic ending, involving recombination of heavily mutated RNA fragments of the virus, with the possible inference of a distinct helper virus. This would indicate that the SARS-CoV2 is under very strong evolutionary pressure, possibly marking the end of the pandemic. Remarkably, it is observed that the density of OMICRON mutations in the SPIKE PRION region is more than 8 times that of the rest of the Spike protein. This high density of mutations of the Prion region in OMICRON appears to completely suppress this possible Prion function, unlike the Spikes of the various variants and mRNAs vaccines where this Prion function is observed. ADDENDUM by Pr Luc Montagnier "A big step towards understanding Nature. Your work gives us hope that we will soon emerge from the nightmare where the Cretinoid branch of Humanity plunges us”
... Brojne pojave reaktivacije latentnog herpesa zostera sugeriraju da ta cjepiva dovode do supresije urođenog imunosnog sustava [49] što sugerira i jedno drugo nerecenzirano istraživanje [711]. [49,713,714]. Prioni su pogrešno savijeni i/ili fragmentirani proteini koji obilježavaju izrazito progresivne i uvijek smrtonosne neurodegenerativne bolesti. U tom kontekstu zabrinjava da je Pfizer u svojoj dokumentaciji poslanoj Europskoj agenciji za lijekove (EMA-i) za odobrenje cjepiva naveo da u njegovim injekcijama postoje "fragmentirani specijesi" virusne RNK te da je u injekcijama korištenima za klinička ispitivanja bilo znatno manje tih "fragmentiranih specijesa" u injekcijama. ...
Preprint
Full-text available
U hrvatskim je medijima sve više govora o cijepljenju djece protiv covid-19, unatoč maloj ulozi djece u prijenosu novog koronavirusa i njihovom malom riziku od teških simptoma, postojanju drugih oblika prevencije, činjenici da klinička ispitivanja nisu dovršena, raznih problema u provedenim ispitivanjima i rastućoj zabrinutosti oko sigurnosti cjepiva i mogućih štetnih učinaka. Cilj je ovog kratkog pregleda odabrane znanstvene literature potaknuti kvalitetnu javnu raspravu prije donošenja potencijalno ishitrenih odluka.
... [362][363][364] SARS-CoV-2 Spike has a prion-like domain that enhances its infectiousness. [365][366][367] The Spike S1 RBD may bind to heparin-binding proteins and promote amyloid aggregation. In humans, this could lead to Parkinson's, Lewy Body Dementia, premature Alzheimer's, or various other neurodegenerative diseases. ...
Preprint
Full-text available
An anonymously posted document by someone calling themselves "Spartacus" of the Institute for Coronavirus Emergence Nonprofit Intelligence (ICENI) has been gaining widespread attention. Zero Hedge called the letter "simply the best document I've seen on COVID, vaccines, etc. Whoever Spartacus is, they have a very elaborate knowledge in the field." Layman may want to skip the explanations about "Pathophysiology" and "Vaccine Dangers" since they are very technical. However, the summary and the parts called "Treatments", "Transmission," "Criminal Conspiracy" as well as "Vaccine Development and Links to Transhumanism" can and should be read by everyone.
... The molecular docking studies further suggest that the interaction of the S-protein with prion protein is stronger than with amyloid beta, tau or αsynuclein [5]. In addition, like other prion proteins, the Sprotein also contains several prionogenic domains (PrDs) [6]. Thus, a direct toxic action of the S-protein, triggering a neurodegenerative condition mimicking a prion diseaselike pathology is also a possibility. ...
... The use of prion mechanisms for a fast regulation of gene expression might help viruses to quickly respond to the response to their presence elicited by host. Hence, we anticipate that more viral prion-like proteins will be discovered soon and indeed a recent study suggests that a PrLD in the SARS-CoV-2 spike protein might influence the affinity of this viral protein for angiotensin-converting enzyme 2 in human host cells [130]. ...
Article
Full-text available
Prions are self‐perpetuating proteins able to switch between a soluble state and an aggregated‐and‐transmissible conformation. These proteinaceous entities have been widely studied in yeast, where they are involved in hereditable phenotypic adaptations. The notion that such proteins could play functional roles and be positively selected by evolution has triggered the development of computational tools to identify prion‐like proteins in different kingdoms of life. These algorithms have succeeded in screening multiple proteomes, allowing the identification of prion‐like proteins in a diversity of unrelated organisms, evidencing that the prion phenomenon is well conserved among species. Interestingly enough, prion‐like proteins are not only connected with the formation of functional membraneless protein‐nucleic acid coacervates, but are also linked to human diseases. This review addresses state‐of‐the‐art computational approaches to identify prion‐like proteins, describes proteome‐wide analysis efforts, discusses these unique proteins' functional role, and illustrates recently validated examples in different domains of life.
Article
Full-text available
COVID-19 has shown higher virulence compared to the previous coronavirus epidemics and has shown that it causes damages to the nervous system. In the present study, PrionW web server was used to predict the prion-like domains (PrLDs) in 15 structural and non-structural proteins of SARS-CoV, MERS-CoV and SARS-CoV-2. Among all of these proteins, the results demonstrated one PrLD with the sequence 951EDDYQGKPLEFGATSAALQPEEEQEEDWLDDDSQQTVGQQDGSEDNQTTTIQTIVEVQPQL1012, having an amyloid-core of 988GQQDGSEDNQTTTIQTIVEVQ1009 in the non-structural protein of SARS-CoV-2 with pWALTZ_Score of 59.9936. The sequence of SARS-CoV-2 polyprotein was further investigated by FoldIndex© tool, and a negative fold index was demonstrated at the site of predicted prion-like domain. Multiple sequence alignment of this region with non-structural proteins of SARS-CoV and MERS-CoV, showed that there is no sequence similarity between this predicted region and the corresponding regions of two other viruses. Considering the high similarity between polyproteins of SARS-CoV-2 and SARS-CoV, and their ability to affect the nervous system, it could be suggested that a potential PrLD might be added to SARS-CoV polyprotein.
Article
Full-text available
The outbreak of Coronavirus Disease 2019 (COVID-19) has posed a serious threat to global public health, calling for the development of safe and effective prophylactics and therapeutics against infection of its causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV). The CoV spike (S) protein plays the most important roles in viral attachment, fusion and entry, and serves as a target for development of antibodies, entry inhibitors and vaccines. Here, we identified the receptor-binding domain (RBD) in SARS-CoV-2 S protein and found that the RBD protein bound strongly to human and bat angiotensin-converting enzyme 2 (ACE2) receptors. SARS-CoV-2 RBD exhibited significantly higher binding affinity to ACE2 receptor than SARS-CoV RBD and could block the binding and, hence, attachment of SARS-CoV-2 RBD and SARS-CoV RBD to ACE2-expressing cells, thus inhibiting their infection to host cells. SARS-CoV RBD-specific antibodies could cross-react with SARS-CoV-2 RBD protein, and SARS-CoV RBD-induced antisera could cross-neutralize SARS-CoV-2, suggesting the potential to develop SARS-CoV RBD-based vaccines for prevention of SARS-CoV-2 and SARS-CoV infection.
Article
Full-text available
The outbreak of 2019-novel coronavirus disease (COVID-19) that is caused by SARS-CoV-2 has spread rapidly in China, and has developed to be a Public Health Emergency of International Concern. However, no specific antiviral treatments or vaccines are available yet. This work aims to share strategies and candidate antigens to develop safe and effective vaccines against SARS-CoV-2.
Article
Full-text available
After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus causes acute lung symptoms, leading to a condition that has been named as “coronavirus disease 2019” (COVID-19). The emergence of SARS-CoV-2 and of SARS-CoV caused widespread fear and concern and has threatened global health security. There are some similarities and differences in the epidemiology and clinical features between these two viruses and diseases that are caused by these viruses. The goal of this work is to systematically review and compare between SARS-CoV and SARS-CoV-2 in the context of their virus incubation, originations, diagnosis and treatment methods, genomic and proteomic sequences, and pathogenic mechanisms.
Article
Full-text available
Structure of the nCoV trimeric spike The World Health Organization has declared the outbreak of a novel coronavirus (2019-nCoV) to be a public health emergency of international concern. The virus binds to host cells through its trimeric spike glycoprotein, making this protein a key target for potential therapies and diagnostics. Wrapp et al. determined a 3.5-angstrom-resolution structure of the 2019-nCoV trimeric spike protein by cryo–electron microscopy. Using biophysical assays, the authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor. They also tested three antibodies known to bind to the SARS-CoV spike protein but did not detect binding to the 2019-nCoV spike protein. These studies provide valuable information to guide the development of medical counter-measures for 2019-nCoV. Science , this issue p. 1260
Article
Full-text available
A mysterious outbreak of atypical pneumonia in late 2019 was traced to a seafood wholesale market in Wuhan of China. Within a few weeks, a novel coronavirus tentatively named as 2019 novel coronavirus (2019-nCoV) was announced by the World Health Organization. We performed bioinformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes. Overall, the genome of 2019-nCoV has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV. The phylogenetic trees of their orf1a/b, Spike, Envelope, Membrane and Nucleoprotein also clustered closely with those of the bat, civet and human SARS coronaviruses. However, the external subdomain of Spike’s receptor binding domain of 2019-nCoV shares only 40% amino acid identity with other SARS-related coronaviruses. Remarkably, its orf3b encodes a completely novel short protein. Furthermore, its new orf8 likely encodes a secreted protein with an alpha-helix, following with a beta-sheet(s) containing six strands. Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection.
Article
Full-text available
Advances in genomics and proteomics have revealed eukaryotic proteomes to be highly abundant in intrinsically disordered proteins that are susceptible to diverse post-translational modifications. Intrinsically disordered regions are critical to the liquid–liquid phase separation that facilitates specialized cellular functions. Here, we discuss how post-translational modifications of intrinsically disordered protein segments can regulate the molecular condensation of macromolecules into functional phase-separated complexes.
Article
Full-text available
The etiopathogenesis of type 1 diabetes (T1D), a common autoimmune disorder, is not completely understood. Recent studies suggested the gut microbiome plays a role in T1D. We have used public longitudinal microbiome data from T1D patients to analyze amyloid-producing bacterial composition and found a significant association between initially high amyloid-producing Escherichia coli abundance, subsequent E. coli depletion prior to seroconversion, and T1D development. In children who presented seroconversion or developed T1D, we observed an increase in the E. coli phage/E. coli ratio prior to E. coli depletion, suggesting that the decrease in E. coli was due to prophage activation. Evaluation of the role of phages in amyloid release from E. coli biofilms in vitro suggested an indirect role of the bacterial phages in the modulation of host immunity. This study for the first time suggests that amyloid-producing E. coli, their phages, and bacteria-derived amyloid might be involved in pro-diabetic pathway activation in children at risk for T1D.
Article
Full-text available
Prions are proteins that can self-propagate, leading to the misfolding of proteins. In addition to the previously demonstrated pathogenic roles of prions during the development of different mammalian diseases, including neurodegenerative diseases, they have recently been shown to represent an important functional component in many prokaryotic and eukaryotic organisms and bacteriophages, confirming the previously unexplored important regulatory and functional roles. However, an in-depth analysis of these domains in eukaryotic viruses has not been performed. Here, we examined the presence of prion-like proteins in eukaryotic viruses that play a primary role in different ecosystems and that are associated with emerging diseases in humans. We identified relevant functional associations in different viral processes and regularities in their presence at different taxonomic levels. Using the prion-like amino-acid composition computational algorithm, we detected 2679 unique putative prion-like domains within 2,742,160 publicly available viral protein sequences. Our findings indicate that viral prion-like proteins can be found in different viruses of insects, plants, mammals, and humans. The analysis performed here demonstrated common patterns in the distribution of prion-like domains across viral orders and families, and revealed probable functional associations with different steps of viral replication and interaction with host cells. These data allow the identification of the viral prion-like proteins as potential novel regulators of viral infections.
Article
Full-text available
Both severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are zoonotic pathogens that crossed the species barriers to infect humans. The mechanism of viral interspecies transmission is an important scientific question to be addressed. These coronaviruses contain a surface-located spike (S) protein that initiates infection by mediating receptor-recognition and membrane fusion and is therefore a key factor in host specificity. In addition, the S protein needs to be cleaved by host proteases before executing fusion, making these proteases a second determinant of coronavirus interspecies infection. Here, we summarize the progress made in the past decade in understanding the cross-species transmission of SARS-CoV and MERS-CoV by focusing on the features of the S protein, its receptor-binding characteristics, and the cleavage process involved in priming. Copyright © 2015 Elsevier Ltd. All rights reserved.
Article
Full-text available
Coronaviruses (CoVs), enveloped positive-sense RNA viruses, are characterized by club-like spikes that project from their surface, an unusually large RNA genome, and a unique replication strategy. Coronaviruses cause a variety of diseases in mammals and birds ranging from enteritis in cows and pigs and upper respiratory disease in chickens to potentially lethal human respiratory infections. Here we provide a brief introduction to coronaviruses discussing their replication and pathogenicity, and current prevention and treatment strategies. We also discuss the outbreaks of the highly pathogenic Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the recently identified Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV).
Article
Full-text available
Today's graphics processing units (GPUs) compose the scene from individual triangles. As about 320 triangles are needed to approximate a single sphere—an atom—in a convincing way, visualizing larger proteins with atomic details requires tens of millions of triangles, far too many for smooth interactive frame rates. We describe a new approach to solve this ‘molecular graphics problem’, which shares the work between GPU and multiple CPU cores, generates high-quality results with perfectly round spheres, shadows and ambient lighting and requires only OpenGL 1.0 functionality, without any pixel shader Z-buffer access (a feature which is missing in most mobile devices). Availability and implementation: YASARA View, a molecular modeling program built around the visualization algorithm described here, is freely available (including commercial use) for Linux, MacOS, Windows and Android (Intel) from www.YASARA.org. Contact: elmar@yasara.org Supplementary information: Supplementary data are available at Bioinformatics online.
Article
Full-text available
Prions are self-templating protein aggregates that stably perpetuate distinct biological states and are of keen interest to researchers in both evolutionary and biomedical science. The best understood prions are from yeast and have a prion-forming domain with strongly biased amino acid composition, most notably enriched for Q or N. PLAAC is a web application that scans protein sequences for domains with P: rion-L: ike A: mino A: cid C: omposition. Users can upload sequence files, or paste sequences directly into a textbox. PLAAC ranks the input sequences by several summary scores and allows scores along sequences to be visualized. Text output files can be downloaded for further analyses, and visualizations saved in PDF and PNG formats. Availability and Implementation: http://plaac.wi.mit.edu/. The Ruby-based web framework, and the command-line software (implemented in Java, with visualization routines in R) are available at: http://github.com/whitehead/plaac under the MIT license. All software can be run under OS X, Windows, and Unix. oliver.king@umassmed.edu, lindquist_admin@wi.mit.edu.
Article
The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen that was first identified in humans in Saudi Arabia and Jordan in 2012. Intermittent sporadic cases, community clusters, and nosocomial outbreaks of MERS-CoV continue to occur. Between April 2012 and December 2019, 2499 laboratory-confirmed cases of MERS-CoV infection, including 858 deaths (34·3% mortality) were reported from 27 countries to WHO, the majority of which were reported by Saudi Arabia (2106 cases, 780 deaths). Large outbreaks of human-to-human transmission have occurred, the largest in Riyadh and Jeddah in 2014 and in South Korea in 2015. MERS-CoV remains a high-threat pathogen identified by WHO as a priority pathogen because it causes severe disease that has a high mortality rate, epidemic potential, and no medical countermeasures. This Seminar provides an update on the current knowledge and perspectives on MERS epidemiology, virology, mode of transmission, pathogenesis, diagnosis, clinical features, management, infection control, development of new therapeutics and vaccines, and highlights unanswered questions and priorities for research, improved management, and prevention.
Article
Coronavirus disease (COVID-19) is caused by SARS-COV2 and represents the causative agent of a potentially fatal disease that is of great global public health concern. Based on the large number of infected people that were exposed to the wet animal market in Wuhan City, China, it is suggested that this is likely the zoonotic origin of COVID-19. Person-to-person transmission of COVID-19 infection led to the isolation of patients that were subsequently administered a variety of treatments. Extensive measures to reduce person-to-person transmission of COVID-19 have been implemented to control the current outbreak. Special attention and efforts to protect or reduce transmission should be applied in susceptible populations including children, health care providers, and elderly people. In this review, we highlights the symptoms, epidemiology, transmission, pathogenesis, phylogenetic analysis and future directions to control the spread of this fatal disease.
Article
Numerous proteins contain domains that are enriched in glutamine and asparagine residues, and aggregation of some of these proteins has been linked to both prion formation in yeast and a number of human diseases. Unfortunately, predicting whether a given glutamine/asparagine-rich protein will aggregate has proven difficult. Here we describe a recently developed algorithm designed to predict the aggregation propensity of glutamine/asparagine-rich proteins. We discuss the basis for the algorithm, its limitations, and usage of recently developed online and downloadable versions of the algorithm.
Article
Glutamine/asparagine (Q/N)-rich domains have a high propensity to form self-propagating amyloid fibrils. This phenomenon underlies both prion-based inheritance in yeast and aggregation of a number of proteins involved in human neurodegenerative diseases. To examine the prevalence of this phenomenon, complete proteomic sequences of 31 organisms and several incomplete proteomic sequences were examined for Q/N-rich regions. We found that Q/N-rich regions are essentially absent from the thermophilic bacterial and archaeal proteomes. Moreover, the average Q/N content of the proteins in these organisms is markedly lower than in mesophilic bacteria and eukaryotes. Mesophilic bacterial proteomes contain a small number (0-4) of proteins with Q/N-rich regions. Remarkably, Q/N-rich domains are found in a much larger number of eukaryotic proteins (107-472 per proteome) with diverse biochemical functions. Analyses of these regions argue they have been evolutionarily selected perhaps as modular "polar zipper" protein-protein interaction domains. These data also provide a large pool of potential novel prion-forming proteins, two of which have recently been shown to behave as prions in yeast, thus suggesting that aggregation or prion-like regulation of protein function may be a normal regulatory process for many eukaryotic proteins with a wide variety of functions.
Article
Recent evidence indicates that diverse neurodegenerative diseases might have a common cause and pathological mechanism — the misfolding, aggregation and accumulation of proteins in the brain, resulting in neuronal apoptosis. Studies from different disciplines strongly support this hypothesis and indicate that a common therapy for these devastating disorders might be possible. The aim of this article is to review the literature on the molecular mechanism of protein misfolding and aggregation, its role in neurodegeneration and the potential targets for therapeutic intervention in neurodegenerative diseases. Many questions still need to be answered and future research in this field will result in exciting new discoveries that might impact other areas of biology.
Article
Amyloid--a fibrillar, cross beta-sheet quaternary structure--was first discovered in the context of human disease and tissue damage, and was thought to always be detrimental to the host. Recent studies have identified amyloid fibers in bacteria, fungi, insects, invertebrates and humans that are functional. For example, human Pmel17 has important roles in the biosynthesis of the pigment melanin, and the factor XII protein of the hemostatic system is activated by amyloid. Functional amyloidogenesis in these systems requires tight regulation to avoid toxicity. A greater understanding of the diverse physiological applications of this fold has the potential to provide a fresh perspective for the treatment of amyloid diseases.
The ACE2 Expression in Sertoli cells and Germ cells may cause male reproductive disorder after SARS-CoV-2 Infection
  • Q Shen
  • X Xiao
  • A Aierken
  • M Liao
  • J Hua
Shen, Q., Xiao, X., Aierken, A., Liao, M. and Hua, J., 2020. The ACE2 Expression in Sertoli cells and Germ cells may cause male reproductive disorder after SARS-CoV-2 Infection.
  • G Tetz
  • M Pinho
  • S Pritzkow
  • N Mendez
  • C Soto
  • V Tetz
Tetz, G., Pinho, M., Pritzkow, S., Mendez, N., Soto, C. and Tetz, V., 2020. Bacterial DNA promotes Tau aggregation. Scientific Reports, 10(1), pp.1-11.