Abstract：
:The development of computational strategies for the quantitative characterization of the functional mechanisms of SARS-CoV-2 spike proteins is of paramount importance in efforts to accelerate the discovery of novel therapeutic agents and vaccines combating the COVID-19 pandemic. Structural and biophysical studies have recently characterized the conformational landscapes of the SARS-CoV-2 spike glycoproteins in the prefusion form, revealing a spectrum of stable and more dynamic states. By employing molecular simulations and network modeling approaches, this study systematically examined functional dynamics and identified the regulatory centers of allosteric interactions for distinct functional states of the wild-type and mutant variants of the SARS-CoV-2 prefusion spike trimer. This study presents evidence that the SARS-CoV-2 spike protein can function as an allosteric regulatory engine that fluctuates between dynamically distinct functional states. Perturbation-based modeling of the interaction networks revealed a key role of the cross-talk between the effector hotspots in the receptor binding domain and the fusion peptide proximal region of the SARS-CoV-2 spike protein. The results have shown that the allosteric hotspots of the interaction networks in the SARS-CoV-2 spike protein can control the dynamic switching between functional conformational states that are associated with virus entry to the host receptor. This study offers a useful and novel perspective on the underlying mechanisms of the SARS-CoV-2 spike protein through the lens of allosteric signaling as a regulatory apparatus of virus transmission that could open up opportunities for targeted allosteric drug discovery against SARS-CoV-2 proteins and contribute to the rapid response to the current and potential future pandemic scenarios.
journal_name
J Proteome Resjournal_title
Journal of proteome researchauthors
Verkhivker GMdoi
10.1021/acs.jproteome.0c00654subject
Has Abstractpub_date
2020-11-06 00:00:00pages
4587-4608issue
11eissn
1535-3893issn
1535-3907journal_volume
19pub_type
杂志文章abstract：:Oxidative injury is believed to play an important role in the pathogenesis of lung diseases such as emphysema and lung cancer. We examined the effects of a classic reactive oxygen species, H 2O 2, on the hydrogen peroxide response proteins (HPRP) in human pneumocytes using comparative two-dimensional gel electrophores...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr800295j
更新日期：2008-11-01 00:00:00
abstract：:Recombinant virus-like particles (VLPs) have been shown to induce protective immunity. Despite their potential significance as promising vaccine candidates, the protein composition of VLPs produced in insect cells has not been well characterized. Here we report a proteomic analysis of influenza VLPs containing hemaggl...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr200086v
更新日期：2011-08-05 00:00:00
abstract：:Isobaric tagging is the method of choice in mass-spectrometry-based proteomics for comparing several conditions at a time. Despite its multiplexing capabilities, some drawbacks appear when multiple experiments are merged for comparison in large sample-size studies due to the presence of missing values, which result fr...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.8b00110
更新日期：2018-06-01 00:00:00
abstract：:Adipose tissue is a major storage site for lipophilic environmental contaminants. The environmental metabolic disruptor hypothesis postulates that some pollutants can promote obesity or metabolic disorders by activating nuclear receptors involved in the control of energetic homeostasis. In this context, monoethylhexyl...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr200765v
更新日期：2011-12-02 00:00:00
abstract：:Method development is one of the objectives of the astrophysical community for characterizing the organic matter in objects of the solar system. In this context, we report on the development of an enzyme-catalyzed stereoselective hydrolysis, inspired by the proteomics discipline, which has enabled the indirect detecti...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.0c00700
更新日期：2020-10-20 00:00:00
abstract：:The International Mouse Phenotyping Consortium program has been established to ascribe biological functions to systematically knocked-out (KO) genes by in vivo and ex vivo phenotyping. The plasma clinical chemistry screen includes an assessment of liver, kidney, and bone function and provides a basic lipid profile and...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr501039k
更新日期：2015-05-01 00:00:00
abstract：:The present study reports an in-depth proteome analysis of two Lactobacillus rhamnosus strains, the well-known probiotic strain GG and the dairy strain Lc705. We used GeLC-MS/MS, in which proteins are separated using 1-DE and identified using nanoLC-MS/MS, to generate high-quality protein catalogs. To maximize the num...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr2000896
更新日期：2011-08-05 00:00:00
abstract：:Membrane proteins play a critical role in the process of neural stem cell self-renewal and differentiation. Here, we apply the SILAC (stable isotope labeling by amino acids in cell culture) approach to quantitatively compare the membrane proteome of the self-renewing and the astroglial differentiating cells. High-reso...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr200677z
更新日期：2012-02-03 00:00:00
abstract：:Chronic kidney disease (CKD) has emerged as a major public health problem worldwide. It frequently progresses to end-stage renal disease, which is related to very high cost and mortality. Novel biomarkers can provide insight into the novel mechanism, facilitate early detection, and monitor progression of CKD and its r...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.6b00583
更新日期：2016-10-07 00:00:00
abstract：:We investigated possible associations between sequence evolution of mammalian sperm proteins and their phosphorylation status in humans. As a reference, spermatozoa from three normozoospermic men were analyzed combining two-dimensional gel electrophoresis, immunoblotting, and mass spectrometry. We identified 99 sperm ...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr400228c
更新日期：2013-12-06 00:00:00
abstract：:The chromatophore membrane of the photosynthetic diazotroph Rhodospirillum rubrum is of vital importance for a number of central processes, including nitrogen fixation. Using a novel amphiphile, we have identified protein complexes present under different nitrogen availability conditions by the use of two-dimensional ...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr100838x
更新日期：2011-06-03 00:00:00
abstract：:Compartment proteomics enable broad characterization of target tissues. We employed a simple fractionation method and filter-aided sample preparation (FASP) to characterize the cytosolic and membrane fractions of white perch ovary tissues by semiquantitative tandem mass spectrometry using label-free quantitation based...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr401067g
更新日期：2014-03-07 00:00:00
abstract：:A comprehensive study of the molecular active landscape of human cells can be undertaken to integrate two different but complementary perspectives: transcriptomics, and proteomics. After the genome era, proteomics has emerged as a powerful tool to simultaneously identify and characterize the compendium of thousands of...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.5b00474
更新日期：2015-09-04 00:00:00
abstract：:Porphyromonas gingivalis is a keystone periodontal pathogen that has been associated with autoimmune disorders. The cell surface proteases Lys-gingipain (Kgp) and Arg-gingipains (RgpA and RgpB) are major virulence factors, and their proteolytic activity is enhanced by small peptides such as glycylglycine (GlyGly). The...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.8b00286
更新日期：2018-08-03 00:00:00
abstract：:Plastids are essential organelles because they contribute to primary and secondary metabolism and plant signaling networks. A high-quality inventory of the plastid proteome is therefore a critical tool in plant research. We present reference plastid proteomes for maize (Zea mays) and Arabidopsis (Arabidopsis thaliana)...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr300952g
更新日期：2013-01-04 00:00:00
abstract：:Incomplete recovery from the LC column is identified as a major cause for poor detection efficiency of phosphopeptides by LC-MS/MS. It is proposed that metal ions adsorbed on the stationary phase interact with the phosphate group of phosphopeptides via an ion-pairing mechanism related to IMAC (IMAC: immobilized metal ...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr800304n
更新日期：2009-01-01 00:00:00
abstract：:Genetically identical cloned pigs should in principle eliminate biological variation and provide more pronounced effects when subjected to, e.g., dietary interventions, but little is known about how phenotype and phenotypic variation is affected by cloning. Therefore, an investigation of the metabolome of cloned pigs ...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr201253h
更新日期：2012-07-06 00:00:00
abstract：:Large-scale metabolomics studies involving thousands of samples present multiple challenges in data analysis, particularly when an untargeted platform is used. Studies with multiple cohorts and analysis platforms exacerbate existing problems such as peak alignment and normalization. Therefore, there is a need for robu...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.6b00125
更新日期：2016-12-02 00:00:00
abstract：:Herein, we report on the venom proteome of Vipera anatolica senliki, a recently discovered and hitherto unexplored subspecies of the critically endangered Anatolian meadow viper endemic to the Antalya Province of Turkey. Integrative venomics, including venom gland transcriptomics as well as complementary bottom-up and...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.9b00869
更新日期：2020-04-03 00:00:00
abstract：:The CB1 and CB2 cannabinoid receptors belong to the GPCR superfamily and are associated with a variety of physiological and pathophysiological processes. Both receptors, with several lead compounds at different phases of development, are potentially useful targets for drug discovery. For this reason, fully elucidating...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr060671h
更新日期：2007-06-01 00:00:00
abstract：:In Thailand, diabetes mellitus is the most significant risk factor for melioidosis, a severe disease caused by Burkholderia pseudomallei. In this study, neutrophils isolated from healthy or diabetic subjects were infected with B. thailandensis E555, a variant strain with a B. pseudomallei-like capsular polysaccharide ...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.9b00166
更新日期：2019-07-05 00:00:00
abstract：:Decoy database searches are used to filter out false positive protein identifications derived from search engines, but there is no consensus about which decoy is "the best". We evaluate nine different decoy designs using public data sets from samples of known composition. Statistically significant performance differen...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr800792z
更新日期：2009-04-01 00:00:00
abstract：:Bacillus Amyloliquefaciens SQR9 is a well-investigated plant growth-promoting rhizobacteria with strong root colonization capability. To identify the key proteins involved in in situ root colonization and biofilm formation, the proteomic profiles of planktonic and root colonized SQR9 cells were compared. A total of 75...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr500565m
更新日期：2014-12-05 00:00:00
abstract：:Workflows for large-scale (MS)-based shotgun proteomics can potentially lead to costly errors in the form of incorrect peptide-spectrum matches (PSMs). To improve the robustness of these workflows, we have investigated the use of the precursor mass discrepancy (PMD) to detect and filter potentially false PSMs that hav...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.9b00478
更新日期：2020-01-03 00:00:00
abstract：:There is a legion of hypothetical proteins (HP) in prokaryotic and eukaryotic proteomes and the aim of this study was to describe HP in the perireticular nucleus (PN), a key structure in human brain development. Tissue from four PNs was homogenized and extracted proteins were run on two-dimensional gel electrophoresis...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr050133p
更新日期：2005-11-01 00:00:00
abstract：:As a potential tool for proteomics and protein characterization, in-gel cysteine- and arginine-specific cleavage is demonstrated by means of trypsin or endoproteinase Lys-C for six model proteins (lysozyme, alpha-lactalbumin, beta-lactoglobulin, ribonuclease A, albumin, and transferrin), ranging in size from 14 kDa to...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr025568g
更新日期：2003-03-01 00:00:00
abstract：:Although the "missing protein" is a temporary concept in C-HPP, the biological information for their "missing" could be an important clue in evolutionary studies. Here we classified missing-protein-encoding genes into two groups, the genes encoding PE2 proteins (with transcript evidence) and the genes encoding PE3/4 p...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.5b00450
更新日期：2015-12-04 00:00:00
abstract：:Metabolomic approaches have the potential to make an exceptional contribution to understanding how chemicals and other environmental stressors can affect both human and environmental health. However, the application of metabolomics to environmental exposures, although getting underway, has not yet been extensively exp...
journal_title：Journal of proteome research
pub_type： 杂志文章,评审
doi：10.1021/pr060623x
更新日期：2007-02-01 00:00:00
abstract：:Clostridioides difficile-associated infection (CDI) is a health-care-associated infection caused, as the name suggests, by obligate anaerobic pathogen C. difficile and thus mainly transmitted via highly resistant endospores from one person to the other. In vivo, the spores need to germinate into cells prior to establi...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/acs.jproteome.9b00413
更新日期：2019-11-01 00:00:00
abstract：:The Model Organism Protein Expression Database (MOPED, http://moped.proteinspire.org) is an expanding proteomics resource to enable biological and biomedical discoveries. MOPED aggregates simple, standardized and consistently processed summaries of protein expression and metadata from proteomics (mass spectrometry) ex...
journal_title：Journal of proteome research
pub_type： 杂志文章
doi：10.1021/pr400884c
更新日期：2014-01-03 00:00:00
