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10.1126/scisignal.abd0334 http://scihub22266oqcxt.onion/10.1126/scisignal.abd0334 33436497!7928535!33436497     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=33436497&cmd=llinks): Failed to open stream: HTTP request failed! 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Short linear motif candidates in the cell entry system used by SARS-CoV-2 and their potential therapeutic implications |pdf=|usr=}}{{33436497}} gab.com Text Short linear motif candidates in the cell entry system used by SARS-CoV-2 and their potential therapeutic implications JO: Sci Signal http://www.kidney.de/pget.php?&tw=1&pmid=33436497 #FOAvip The first reported receptor for SARS-CoV-2 on host cells was the angiotensin-converting enzyme 2 (ACE2). However, the viral spike protein also has an RGD motif, suggesting that cell surface integrins may be co-receptors. We examined the sequences of ACE2 and integrins with the Eukaryotic Linear Motif (ELM) resource and identified candidate short linear motifs (SLiMs) in their short, unstructured, cytosolic tails with potential roles in endocytosis, membrane dynamics, autophagy, cytoskeleton, and cell signaling. These SLiM candidates are highly conserved in vertebrates and may interact with the mu2 subunit of the endocytosis-associated AP2 adaptor complex, as well as with various protein domains (namely, I-BAR, LC3, PDZ, PTB, and SH2) found in human signaling and regulatory proteins. Several motifs overlap in the tail sequences, suggesting that they may act as molecular switches, such as in response to tyrosine phosphorylation status. Candidate LC3-interacting region (LIR) motifs are present in the tails of integrin beta(3) and ACE2, suggesting that these proteins could directly recruit autophagy components. Our findings identify several molecular links and testable hypotheses that could uncover mechanisms of SARS-CoV-2 attachment, entry, and replication against which it may be possible to develop host-directed therapies that dampen viral infection and disease progression. Several of these SLiMs have now been validated to mediate the predicted peptide interactions. Twit Text FOAVip Short linear motif candidates in the cell entry system used by SARS-CoV-2 and their potential therapeutic implications ????Sci Signal http://www.kidney.de/pget.php?&tw=1&pmid=33436497 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33436497 #FOAvip English Wikipedia <ref>{{Cite pmid|33436497}}</ref> Short linear motif candidates in the cell entry system used by SARS-CoV-2 and their potential therapeutic implications #MMPMID33436497 Meszaros B; Samano-Sanchez H; Alvarado-Valverde J; Calyseva J; Martinez-Perez E; Alves R; Shields DC; Kumar M; Rippmann F; Chemes LB; Gibson TJ Sci Signal 2021[Jan]; 14 (665): ä PMID33436497show ga The first reported receptor for SARS-CoV-2 on host cells was the angiotensin-converting enzyme 2 (ACE2). However, the viral spike protein also has an RGD motif, suggesting that cell surface integrins may be co-receptors. We examined the sequences of ACE2 and integrins with the Eukaryotic Linear Motif (ELM) resource and identified candidate short linear motifs (SLiMs) in their short, unstructured, cytosolic tails with potential roles in endocytosis, membrane dynamics, autophagy, cytoskeleton, and cell signaling. These SLiM candidates are highly conserved in vertebrates and may interact with the mu2 subunit of the endocytosis-associated AP2 adaptor complex, as well as with various protein domains (namely, I-BAR, LC3, PDZ, PTB, and SH2) found in human signaling and regulatory proteins. Several motifs overlap in the tail sequences, suggesting that they may act as molecular switches, such as in response to tyrosine phosphorylation status. Candidate LC3-interacting region (LIR) motifs are present in the tails of integrin beta(3) and ACE2, suggesting that these proteins could directly recruit autophagy components. Our findings identify several molecular links and testable hypotheses that could uncover mechanisms of SARS-CoV-2 attachment, entry, and replication against which it may be possible to develop host-directed therapies that dampen viral infection and disease progression. Several of these SLiMs have now been validated to mediate the predicted peptide interactions. |*Virus Internalization[MESH] |Amino Acid Sequence[MESH] |Angiotensin-Converting Enzyme 2/chemistry/genetics/physiology[MESH] |Animals[MESH] |COVID-19/therapy/*virology[MESH] |Conserved Sequence[MESH] |Host Microbial Interactions/genetics/*physiology[MESH] |Humans[MESH] |Integrins/chemistry/genetics/physiology[MESH] |Intrinsically Disordered Proteins/chemistry/genetics/physiology[MESH] |Models, Biological[MESH] |Models, Molecular[MESH] |Oligopeptides/chemistry/genetics/physiology[MESH] |Protein Interaction Domains and Motifs/genetics/physiology[MESH] |Protein Sorting Signals/genetics/physiology[MESH] |Receptors, Virus/chemistry/genetics/physiology[MESH] |SARS-CoV-2/genetics/*pathogenicity/*physiology[MESH]Short linear motif candidates in the cell entry system used by SARS-Co(epmc).pdf DeepDyve Pubget Overpricing