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Journal of Basic Microbiology Mar 2021The outbreak of a novel coronavirus associated with acute respiratory disease, called COVID-19, marked the introduction of the third spillover of an animal coronavirus... (Review)
Review
The outbreak of a novel coronavirus associated with acute respiratory disease, called COVID-19, marked the introduction of the third spillover of an animal coronavirus (CoV) to humans in the last two decades. The genome analysis with various bioinformatics tools revealed that the causative pathogen (SARS-CoV-2) belongs to the subgenus Sarbecovirus of the genus Betacoronavirus, with highly similar genome as bat coronavirus and receptor-binding domain (RBD) of spike glycoprotein as Malayan pangolin coronavirus. Based on its genetic proximity, SARS-CoV-2 is likely to have originated from bat-derived CoV and transmitted to humans via an unknown intermediate mammalian host, probably Malayan pangolin. Further, spike protein S1/S2 cleavage site of SARS-CoV-2 has acquired polybasic furin cleavage site which is absent in bat and pangolin suggesting natural selection either in an animal host before zoonotic transfer or in humans following zoonotic transfer. In the current review, we recapitulate a preliminary opinion about the disease, origin and life cycle of SARS-CoV-2, roles of virus proteins in pathogenesis, commonalities, and differences between different corona viruses. Moreover, the crystal structures of SARS-CoV-2 proteins with unique characteristics differentiating it from other CoVs are discussed. Our review also provides comprehensive information on the molecular aspects of SARS-CoV-2 including secondary structures in the genome and protein-protein interactions which can be useful to understand the aggressive spread of the SARS-CoV-2. The mutations and the haplotypes reported in the SARS-CoV-2 genome are summarized to understand the virus evolution.
Topics: Animals; COVID-19; Coronavirus Nucleocapsid Proteins; Genome, Viral; Humans; Pandemics; Phosphoproteins; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Viral Matrix Proteins; Viral Zoonoses; Virus Replication
PubMed: 33460172
DOI: 10.1002/jobm.202000537 -
Cell Apr 2023Negative-stranded RNA viruses can establish long-term persistent infection in the form of large intracellular inclusions in the human host and cause chronic diseases....
Negative-stranded RNA viruses can establish long-term persistent infection in the form of large intracellular inclusions in the human host and cause chronic diseases. Here, we uncover how cellular stress disrupts the metastable host-virus equilibrium in persistent infection and induces viral replication in a culture model of mumps virus. Using a combination of cell biology, whole-cell proteomics, and cryo-electron tomography, we show that persistent viral replication factories are dynamic condensates and identify the largely disordered viral phosphoprotein as a driver of their assembly. Upon stress, increased phosphorylation of the phosphoprotein at its interaction interface with the viral polymerase coincides with the formation of a stable replication complex. By obtaining atomic models for the authentic mumps virus nucleocapsid, we elucidate a concomitant conformational change that exposes the viral genome to its replication machinery. These events constitute a stress-mediated switch within viral condensates that provide an environment to support upregulation of viral replication.
Topics: Humans; Mumps virus; Nucleocapsid; Persistent Infection; Phosphoproteins; Virus Replication
PubMed: 37116470
DOI: 10.1016/j.cell.2023.03.015 -
Molecules (Basel, Switzerland) Dec 2020Phosphonopeptides are phosphorus analogues of peptides and have been widely applied as enzyme inhibitors and antigens to induce catalytic antibodies. Phosphonopeptides... (Review)
Review
Phosphonopeptides are phosphorus analogues of peptides and have been widely applied as enzyme inhibitors and antigens to induce catalytic antibodies. Phosphonopeptides generally contain one aminoalkylphosphonic acid residue and include phosphonopeptides with C-terminal aminoalkylphosphonic acids and phosphonopeptides with a phosphonamidate bond. The phosphonamidate bond in the phosphonopeptides is generally formed via phosphonylation with phosphonochloridates, condensation with coupling reagents and enzymes, and phosphinylation followed by oxidation. Pseudo four-component condensation reaction of amides, aldehydes, alkyl dichlorophosphites, and amino/peptide esters is an alternative, convergent, and efficient strategy for synthesis of phosphonopeptides through simultaneous construction of aminoalkylphosphonic acids and formation of the phosphonamidate bond. This review focuses on the synthetic methods of phosphonopeptides containing a phosphonamidate bond.
Topics: Chemistry Techniques, Synthetic; Chlorides; Halogenation; Organophosphorus Compounds; Oxalates; Peptides; Phosphoproteins
PubMed: 33322827
DOI: 10.3390/molecules25245894 -
Bioengineered Dec 2021Human stanniocalcin 2 (STC2) is an ortholog of fish stanniocalcins (STCs) and is widely expressed in various organs and tissues. The gene is localized on chromosome 5q33... (Review)
Review
Human stanniocalcin 2 (STC2) is an ortholog of fish stanniocalcins (STCs) and is widely expressed in various organs and tissues. The gene is localized on chromosome 5q33 or 5q35. STC2 has been implicated in glucose homeostasis and phosphorus metabolism. It is also reported to be implicated in various malignancies. STC2 was found to be implicated in breast cancer and gynecologic cancers, suggesting hormone-specific or -dependent activities in these malignancies. Moreover, it was reported to be involved in gastrointestinal tumors, including esophageal, gastric, colorectal, and liver cancers, and respiratory cancers, including laryngeal and lung cancers. It also influenced renal carcinoma and prostate cancer. Notably, as a secreted phosphoprotein, STC2 was detectable in serum and possessed promising predictive value in several malignancies. This review aims to improve the understanding of the role of STC2 in patient diagnosis and prognosis, and tumor development and progression, as well as the mechanisms involved.
Topics: Animals; Biomarkers, Tumor; Glycoproteins; Humans; Intercellular Signaling Peptides and Proteins; Mice; Neoplasms; Phosphoproteins
PubMed: 34612765
DOI: 10.1080/21655979.2021.1977551 -
International Journal of Molecular... Nov 2019Reversible protein phosphorylation at serine, threonine and tyrosine is a well-known dynamic post-translational modification with stunning regulatory and signalling... (Review)
Review
Reversible protein phosphorylation at serine, threonine and tyrosine is a well-known dynamic post-translational modification with stunning regulatory and signalling functions in eukaryotes. Shotgun phosphoproteomic analyses revealed that this post-translational modification is dramatically lower in bacteria than in eukaryotes. However, Ser/Thr/Tyr phosphorylation is present in all analysed bacteria (24 eubacteria and 1 archaea). It affects central processes, such as primary and secondary metabolism development, sporulation, pathogenicity, virulence or antibiotic resistance. Twenty-nine phosphoprotein orthologues were systematically identified in bacteria: ribosomal proteins, enzymes from glycolysis and gluconeogenesis, elongation factors, cell division proteins, RNA polymerases, ATP synthases and enzymes from the citrate cycle. While Ser/Thr/Tyr phosphorylation exists in bacteria, there is a consensus that histidine phosphorylation is the most abundant protein phosphorylation in prokaryotes. Unfortunately, histidine shotgun phosphorproteomics is not possible due to the reduced phosphohistidine half-life under the acidic pH conditions used in standard LC-MS/MS analysis. However, considering the fast and continuous advances in LC-MS/MS-based phosphoproteomic methodologies, it is expected that further innovations will allow for the study of His phosphoproteomes and a better coverage of bacterial phosphoproteomes. The characterisation of the biological role of bacterial Ser/Thr/Tyr and His phosphorylations might revolutionise our understanding of prokaryotic physiology.
Topics: Amino Acids; Bacteria; Bacterial Infections; Bacterial Proteins; Chromatography, Liquid; Humans; Phosphoproteins; Phosphorylation; Protein Processing, Post-Translational; Proteomics; Tandem Mass Spectrometry
PubMed: 31766156
DOI: 10.3390/ijms20225678 -
Proteomics Mar 2015Analysis of the phosphoproteome by MS has become a key technology for the characterization of dynamic regulatory processes in the cell, since kinase and phosphatase... (Review)
Review
Analysis of the phosphoproteome by MS has become a key technology for the characterization of dynamic regulatory processes in the cell, since kinase and phosphatase action underlie many major biological functions. However, the addition of a phosphate group to a suitable side chain often confounds informatic analysis by generating product ion spectra that are more difficult to interpret (and consequently identify) relative to unmodified peptides. Collectively, these challenges have motivated bioinformaticians to create novel software tools and pipelines to assist in the identification of phosphopeptides in proteomic mixtures, and help pinpoint or "localize" the most likely site of modification in cases where there is ambiguity. Here we review the challenges to be met and the informatics solutions available to address them for phosphoproteomic analysis, as well as highlighting the difficulties associated with using them and the implications for data standards.
Topics: Phosphopeptides; Phosphoproteins; Proteomics
PubMed: 25475148
DOI: 10.1002/pmic.201400372 -
Physiological Research Nov 2021Cancer is a complex, multifactorial disease that modern medicine ultimately aims to overcome. Downstream of tyrosine kinase 2 (DOK2) is a well-known tumor suppressor... (Review)
Review
Cancer is a complex, multifactorial disease that modern medicine ultimately aims to overcome. Downstream of tyrosine kinase 2 (DOK2) is a well-known tumor suppressor gene, and a member of the downstream protein DOK family of tyrosine kinases. Through a search of original literature indexed in PubMed and other databases, the present review aims to extricate the mechanisms by which DOK2 acts on cancer, thereby identifying more reliable and effective therapeutic targets to promote enhanced methods of cancer prevention and treatment. The review focuses on the role of DOK2 in multiple tumor types in the lungs, intestines, liver, and breast. Additionally, we discuss the potential mechanisms of action of DOK2 and the downstream consequences via the Ras/MPAK/ERK or PI3K/AKT/mTOR signaling pathways.
Topics: Adaptor Proteins, Signal Transducing; Animals; Genes, Tumor Suppressor; Humans; Neoplasms; Phosphoproteins
PubMed: 34505522
DOI: 10.33549/physiolres.934710 -
Current Opinion in Chemical Biology Oct 2015Reversible protein phosphorylation is critically important in biology and medicine. Hundreds of thousands of sites of protein phosphorylation have been discovered but... (Review)
Review
Reversible protein phosphorylation is critically important in biology and medicine. Hundreds of thousands of sites of protein phosphorylation have been discovered but our understanding of the functions of the vast majority of these post-translational modifications is lacking. This review describes several chemical and biochemical methods that are under development and in current use to install phospho-amino acids and their mimics site-specifically into proteins. The relative merits of total chemical synthesis, semisynthesis, and nonsense suppression strategies for studying protein phosphorylation are discussed in terms of technical simplicity, scope, and versatility.
Topics: Animals; Humans; Mutagenesis, Site-Directed; Phosphoproteins; Phosphorylation; Protein Transport; Recombinant Proteins
PubMed: 26196731
DOI: 10.1016/j.cbpa.2015.07.001 -
Cellular and Molecular Life Sciences :... Sep 2017In this review, we summarize computational and experimental data gathered so far showing that structural disorder is abundant within paramyxoviral nucleoproteins (N) and... (Review)
Review
In this review, we summarize computational and experimental data gathered so far showing that structural disorder is abundant within paramyxoviral nucleoproteins (N) and phosphoproteins (P). In particular, we focus on measles, Nipah, and Hendra viruses and highlight both commonalities and differences with respect to the closely related Sendai virus. The molecular mechanisms that control the disorder-to-order transition undergone by the intrinsically disordered C-terminal domain (N) of their N proteins upon binding to the C-terminal X domain (XD) of the homologous P proteins are described in detail. By having a significant residual disorder, N-XD complexes are illustrative examples of "fuzziness", whose possible functional significance is discussed. Finally, the relevance of N-P interactions as promising targets for innovative antiviral approaches is underscored, and the functional advantages of structural disorder for paramyxoviruses are pinpointed.
Topics: Antiviral Agents; Evolution, Molecular; Intrinsically Disordered Proteins; Molecular Chaperones; Nucleoproteins; Paramyxoviridae; Phosphoproteins; Protein Structure, Quaternary; RNA, Viral; Viral Proteins; Virus Replication
PubMed: 28600653
DOI: 10.1007/s00018-017-2556-3 -
Proceedings of the National Academy of... Jun 2021Proteome-wide profiling of protein phosphorylation has been widely used to reveal the underlying mechanism of diverse cellular signaling events. Yet, characterizing...
Proteome-wide profiling of protein phosphorylation has been widely used to reveal the underlying mechanism of diverse cellular signaling events. Yet, characterizing subcellular phosphoproteome with high spatial-temporal resolution has remained challenging. Herein, we developed a subcellular-specific uncaging-assisted biotinylation and mapping of phosphoproteome (SubMAPP) strategy to monitor the phosphorylation dynamics of subcellular proteome in living cells and animals. Our method capitalizes on the genetically encoded bioorthogonal decaging strategy, which enables the rapid activation of subcellular localized proximity labeling biotin ligase through either light illumination or small-molecule triggers. By further adopting an integrated orthogonal pull-down strategy with quantitative mass spectrometry, SubMAPP allowed for the investigation of subcellular phosphoproteome dynamics, revealing the altered phosphorylation patterns of endoplasmic reticulum (ER) luminal proteins under ER stress. Finally, we further expanded the scope of the SubMAPP strategy to primary neuron culture and living mice.
Topics: Amino Acid Sequence; Animals; Endoplasmic Reticulum; HEK293 Cells; Humans; Mice; Neurons; Phosphoproteins; Proteome; Proteomics; Subcellular Fractions; Time Factors
PubMed: 34135121
DOI: 10.1073/pnas.2025299118