The devastating impact of the ongoing coronavirus disease 2019 (COVID-19) on public health, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has made targeting the COVID-19 pandemic a top priority in medical research and pharmaceutical development. Surveillance of SARS-CoV-2 mutations is essential for the comprehension of SARS-CoV-2 variant diversity and their impact on virulence and pathogenicity. The SARS-CoV-2 open reading frame 10 (ORF10) protein interacts with multiple human proteins CUL2, ELOB, ELOC, MAP7D1, PPT1, RBX1, THTPA, TIMM8B, and ZYG11B expressed in lung tissue.
View Article and Find Full Text PDFInt J Biol Macromol
January 2022
Mutations in the titin (TTN) gene are among the most common genomic aberrations in ocular surface squamous neoplasia (OSSN), the most common cancer of the external eye. Further, TTN mutations are associated with resistance to standard therapy with topical interferon alpha-2b (IFN-α2b). However, it remains unclear how TTN mutations drive OSSN pathogenesis and treatment resistance.
View Article and Find Full Text PDFProteins are exposed to fluctuating environmental conditions in their cellular context and during their biotechnological production. Disordered regions are susceptible to these fluctuations and may experience solvent-dependent conformational switches that affect their local dynamism and activity. In a recent study, we modeled the influence of pH in the conformational state of IDPs by exploiting a charge-hydrophobicity diagram that considered the effect of solution pH on both variables.
View Article and Find Full Text PDFManagement of the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has relied in part on the use of personal protective equipment (PPE). Face masks, as a representative example of PPE, have made a particularly significant contribution. However, most commonly used face masks are made of materials lacking inactivation properties against either SARS-CoV-2 or multidrug-resistant bacteria.
View Article and Find Full Text PDFThree dimensional structures of (chymo)trypsin-like proteinase (3CL) from SARS-CoV-2 and SARS-CoV differ at 8 positions. We previously found that the ValLeu, LysArg, PheHis, and AsnLys mutations in these enzymes can change the orientation of the N- and C-terminal domains of 3CL relative to each other, which leads to a change in catalytic activity. This conclusion was derived from the comparison of the structural catalytic core in 169 (chymo)trypsin-like proteinases with the serine/cysteine fold.
View Article and Find Full Text PDFThe purpose of this review is to highlight recent scientific developments and provide an overview of virus self-assembly and viral particle dynamics. Viruses are organized supramolecular structures with distinct yet related features and functions. Plant viruses are extensively used in biotechnology, and virus-like particulate matter is generated by genetic modification.
View Article and Find Full Text PDFNeurodegenerative diseases are a group of debilitating maladies involving protein aggregation. To this day, all advances in neurodegenerative disease therapeutics have helped symptomatically but have not prevented the root cause of the disease, i.e.
View Article and Find Full Text PDFIEEE/ACM Trans Comput Biol Bioinform
April 2023
Intrinsic disorder is common in proteins, plays important roles in protein functionality, and is commonly associated with various human diseases. To have an accurate tool for the annotation of intrinsic disorder in proteins, this paper proposes a novel algorithm, DeepCLD, for sequence-based prediction of intrinsically disordered proteins. This algorithm uses amino acid position specific scoring matrix (PSSM) to capture the intrinsic variability characteristic of sequence patterns, ResNet to preserve feature space structure, and bidirectional CudnnLSTM as recurrent layer to further improve the efficiency.
View Article and Find Full Text PDFRecently, two cases of complete remission of classical Hodgkin lymphoma (cHL) and follicular lymphoma (FL) after SARS-CoV-2 infection were reported. However, the precise molecular mechanism of this rare event is yet to be understood. Here, we hypothesize a potential anti-tumor immune response of SARS-CoV-2 and based on a computational approach show that: (i) SARS-CoV-2 Spike-RBD may bind to the extracellular domains of CD15, CD27, CD45, and CD152 receptors of cHL or FL and may directly inhibit cell proliferation.
View Article and Find Full Text PDFIn recent years, there has been tremendous enthusiasm with respect to detailing the genetic basis of many neoplasms, including conjunctival melanoma (CM). We aim to analyze five proteins associated with CM, namely BRAF, NRAS, c-KIT, NF1, and PTEN. We evaluated each protein for its intrinsically disordered protein regions (IDPRs) and its protein-protein interactions (PPI) with the Predictor of Natural Disordered Protein Regions (PONDR) and the Search Tool for the Retrieval of Interacting Genes (STRING).
View Article and Find Full Text PDFFeatures of the structure and functional activity of bacterial outer membrane porins, coupled with their dynamic "behavior," suggests that intrinsically disordered regions (IDPRs) are contained in their structure. Using bioinformatic analysis, the quantitative content of amyloidogenic regions in the amino acid sequence of non-specific porins inhabiting various natural niches was determined: from terrestrial bacteria of the genus Yersinia (OmpF and OmpC proteins of Y. pseudotuberculosis and Y.
View Article and Find Full Text PDFIntrinsic disorder is a new reality that appears to penetrate every corner of modern protein science. It is difficult to imagine that only 20 years ago the situation was completely different, and almost nobody had heard about 'structure-less' but functional proteins. As a matter of fact, for many at that time, this idea was completely heretical when viewed in light of the then dominating lock-and-key model describing the protein structure-function relationship, where a unique amino acid sequence defines a unique crystal-like 3D structure that serves as a prerequisite for a unique function of a protein.
View Article and Find Full Text PDFMany viruses that cause serious diseases in humans and animals, including the betacoronaviruses (beta-CoVs), such as SARS-CoV, MERS-CoV, and the recently identified SARS-CoV-2, have natural reservoirs in bats. Because these viruses rely entirely on the host cellular machinery for survival, their evolution is likely to be guided by the link between the codon usage of the virus and that of its host. As a result, specific cellular microenvironments of the diverse hosts and/or host tissues imprint peculiar molecular signatures in virus genomes.
View Article and Find Full Text PDFVarious lineages of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have contributed to prolongation of the Coronavirus Disease 2019 (COVID-19) pandemic. Several non-synonymous mutations in SARS-CoV-2 proteins have generated multiple SARS-CoV-2 variants. In our previous report, we have shown that an evenly uneven distribution of unique protein variants of SARS-CoV-2 is geo-location or demography-specific.
View Article and Find Full Text PDFExperimenters face challenges and limitations while analyzing glycoproteins due to their high flexibility, stereochemistry, anisotropic effects, and hydration phenomena. Computational studies complement experiments and have been used in characterization of the structural properties of glycoproteins. However, recent investigations revealed that computational studies face significant challenges as well.
View Article and Find Full Text PDFAlthough vaccination represents the most promising way to stop or contain the coronavirus disease 2019 (COVID-19) pandemic and safety and effectiveness of available vaccines were proven, a small number of individuals who received anti-SARS-CoV-2 vaccines developed a prothrombotic syndrome. Vaccine-induced immune thrombotic thrombocytopenia (VITT) can be triggered by the adenoviral vector-based vaccine, whereas lipid nanoparticle-mRNA-based vaccines can induce rare cases of deep vein thrombosis (DVT). Although the main pathogenic mechanisms behind this rare phenomenon have not yet been identified, both host and vaccine factors might be involved, with pathology at least in part being related to the vaccine-triggered autoimmune reaction.
View Article and Find Full Text PDFAlthough RNA-binding proteins (RBPs) are known to be enriched in intrinsic disorder, no previous analysis focused on RBPs interacting with specific RNA types. We fill this gap with a comprehensive analysis of the putative disorder in RBPs binding to six common RNA types: messenger RNA (mRNA), transfer RNA (tRNA), small nuclear RNA (snRNA), non-coding RNA (ncRNA), ribosomal RNA (rRNA), and internal ribosome RNA (irRNA). We also analyze the amount of putative intrinsic disorder in the RNA-binding domains (RBDs) and non-RNA-binding-domain regions (non-RBD regions).
View Article and Find Full Text PDFWith varying clinical symptoms, most neurodegenerative diseases are associated with abnormal loss of neurons. They share the same common pathogenic mechanisms involving misfolding and aggregation, and these visible aggregates of proteins are deposited in the central nervous system. Amyloid formation is thought to arise from partial unfolding of misfolded proteins leading to the exposure of hydrophobic surfaces, which interact with other similar structures and give rise to form dimers, oligomers, protofibrils, and eventually mature fibril aggregates.
View Article and Find Full Text PDFFor proteins, the sequence → structure → function paradigm applies primarily to enzymes, transmembrane proteins, and signaling domains. This paradigm is not universal, but rather, in addition to structured proteins, intrinsically disordered proteins and regions (IDPs and IDRs) also carry out crucial biological functions. For these proteins, the sequence → IDP/IDR ensemble → function paradigm applies primarily to signaling and regulatory proteins and regions.
View Article and Find Full Text PDFWe have previously demonstrated the ability of the human vaginal strain Lactobacillus crispatus 2029 (LC2029) for strong adhesion to cervicovaginal epithelial cells, expression of the surface layer protein 2 (Slp2), and antagonistic activity against urogenital pathogens. Slp2 forms regular two-dimensional structure around the LC2029 cells,which is secreted into the medium and inhibits intestinal pathogen-induced activation of caspase-9 and caspase-3 in the human intestinal Caco-2 cells. Here, we elucidated the effects of soluble Slp2 on adhesion of proteobacteria pathogens inducing necrotizing enterocolitis (NEC), such as Escherichia coli ATCC E 2348/69, E.
View Article and Find Full Text PDFFavipiravir is a broad-spectrum inhibitor of viral RNA-dependent RNA polymerase (RdRp) currently being used to manage COVID-19. Accumulation of mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RdRp may facilitate antigenic drift, generating favipiravir resistance. Focussing on the chain-termination mechanism utilized by favipiravir, we used high-throughput interface-based protein design to generate > 100 000 designs of the favipiravir-binding site of RdRp and identify mutational hotspots.
View Article and Find Full Text PDFModern protein science is broadening horizons by moving toward the systemic description of proteins in their natural habitats. This implies a transition from a classical reductionist approach associated with consideration of the unique structure and specific biological activity of an individual protein in a purified form to studying entire proteomes and their functions. This minireview provides a brief description of structural, functional, and expression proteomics, the dark proteome (or unfoldome), and some of the tools utilized in the analyses of proteomes.
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