Deep profiling of the cleavage specificity and human substrates of snake venom metalloprotease HF3 by proteomic identification of cleavage site specificity (PICS) using proteome derived peptide libraries and terminal amine isotopic labeling of substrates (TAILS) n-terminomics

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dc.contributorLaboratório de Toxinologia Aplicadapt_BR
dc.contributorCentro de Toxinas, Resposta-imune e Sinalização Celular (CeTICS)pt_BR
dc.contributor.authorPereira, André Zelanis Palitotpt_BR
dc.contributor.authorOliveira, Ana Karina dept_BR
dc.contributor.authorPrudova, Annapt_BR
dc.contributor.authorHuesgen, Pitter F.pt_BR
dc.contributor.authorTashima, Alexandre Keijipt_BR
dc.contributor.authorKizhakkedathu, Jayachandranpt_BR
dc.contributor.authorOverall, Christopher M.pt_BR
dc.contributor.authorSerrano, Solange Maria de Toledopt_BR
dc.date.accessioned2020-08-14T19:55:42Z-
dc.date.available2020-08-14T19:55:42Z-
dc.date.issued2019pt_BR
dc.identifier.citationPereira AZP, Oliveira AK, Prudova A, Huesgen PF., Tashima AK, Kizhakkedathu J, et al. Deep profiling of the cleavage specificity and human substrates of snake venom metalloprotease HF3 by proteomic identification of cleavage site specificity (PICS) using proteome derived peptide libraries and terminal amine isotopic labeling of substrates (TAILS) n-terminomics. J. Proteome Res.. 2019 July;18(9):3419-3428. doi:1535-3907.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/3133-
dc.description.abstractSnakebite is a major medical concern in many parts of the world with metalloproteases playing important roles in the pathological effects of Viperidae venoms, including local tissue damage, hemorrhage, and coagulopathy. Hemorrhagic Factor 3 (HF3), a metalloprotease from Bothrops jararaca venom, induces local hemorrhage and targets extracellular matrix (ECM) components, including collagens and proteoglycans, and plasma proteins. However, the full substrate repertoire of this metalloprotease is unknown. We report positional proteomic studies identifying >2000 N-termini, including neo-N-termini of HF3 cleavage sites in mouse embryonic fibroblast secretome proteins. Terminal amine isotopic labeling of substrates (TAILS) analysis identified a preference for Leu at the P1′ position among candidate HF3 substrates including proteins of the ECM and focal adhesions and the cysteine protease inhibitor cystatin-C. Interestingly, 190 unique peptides matched to annotated cleavage sites in the TopFIND N-termini database, suggesting that these cleavages occurred at a site prone to cleavage or might have been generated by other proteases activated upon incubation with HF3, including caspases-3 and -7, cathepsins D and E, granzyme B, and MMPs 2 and 9. Using Proteomic identification of cleavage site specificity (PICS), a tryptic library derived from THP-1 monocytic cells was used as HF3 substrates for identifying protease cleavage sites and sequence preferences in peptides. A total of 799 unique cleavage sites were detected and, in accordance with TAILS analysis using native secreted protein substrates of MEF cells, revealed a clear preference for Leu at P1′. Taken together, these results greatly expand the known substrate degradome of HF3 and reveal potential new targets, which may serve as a basis to better elucidate the complex pathophysiology of snake envenomation.pt_BR
dc.description.sponsorship(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulopt_BR
dc.description.sponsorship(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológicopt_BR
dc.description.sponsorship(CRC) Canada Research Chairspt_BR
dc.description.sponsorship(MSFHR) Michael Smith Foundation for Health Researchpt_BR
dc.description.sponsorship(CFI) Canada Foundation for Innovationpt_BR
dc.description.sponsorship(CIHR) Canadian Institutes of Health Researchpt_BR
dc.format.extent3419-3428pt_BR
dc.language.isoEnglishpt_BR
dc.relation.ispartofJournal of Proteome Researchpt_BR
dc.titleDeep profiling of the cleavage specificity and human substrates of snake venom metalloprotease HF3 by proteomic identification of cleavage site specificity (PICS) using proteome derived peptide libraries and terminal amine isotopic labeling of substrates (TAILS) n-terminomicspt_BR
dc.typeArticlept_BR
dc.identifier.doi10.1021/acs.jproteome.9b00325pt_BR
dc.identifier.urlhttps://doi.org/10.1021/acs.jproteome.9b00325pt_BR
dc.contributor.externalUniversidade Federal de São Paulo (UNIFESP)pt_BR
dc.contributor.externalUniversity of British Columbia (UBC)pt_BR
dc.identifier.citationvolume18pt_BR
dc.identifier.citationissue9pt_BR
dc.subject.keyworddegradomept_BR
dc.subject.keywordsnake venom metalloproteasept_BR
dc.subject.keywordHF3pt_BR
dc.subject.keywordproteomic identification of cleavage sitespt_BR
dc.subject.keywordPICSpt_BR
dc.subject.keywordterminal amine isotopic labeling of substratespt_BR
dc.subject.keywordTAILSpt_BR
dc.relation.ispartofabbreviatedJ Proteome Respt_BR
dc.identifier.citationabntv. 18, n. 9, p. 3419-3428, jul. 2019pt_BR
dc.identifier.citationvancouver2019 July;18(9):3419-3428pt_BR
dc.contributor.butantanPereira, André Zelanis Palitot|:Aluno|:Laboratório de Toxinologia Aplicada:Centro de Toxinas, Resposta-imune e Sinalização Celular (CeTICS)|:PrimeiroAutorpt_BR
dc.contributor.butantanOliveira, Ana Karina de|:Aluno|:Laboratório de Toxinologia Aplicada:Centro de Toxinas, Resposta-imune e Sinalização Celular (CeTICS)pt_BR
dc.contributor.butantanTashima, Alexandre Keiji|:Aluno|:Laboratório de Toxinologia Aplicada:Centro de Toxinas, Resposta-imune e Sinalização Celular (CeTICS)pt_BR
dc.contributor.butantanSerrano, Solange Maria de Toledo|:Pesquisador:Docente Permanente PPGTOX|:Laboratório de Toxinologia Aplicada:Centro de Toxinas, Resposta-imune e Sinalização Celular (CeTICS)|:Autor de correspondênciapt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2013/07467-1pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2011/23403-8pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2011/08514-8pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2010/17328-0pt_BR
dc.sponsorship.butantanConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)¦¦308133/2015-3)pt_BR
dc.sponsorship.butantanCanada Research Chairs¦¦950-20-3877pt_BR
dc.sponsorship.butantanCanadian Institutes of Health Research (CIHR)¦¦FDN-148408pt_BR
dc.sponsorship.butantanMichael Smith Foundation for Health Research¦¦IN-NPG-0010pt_BR
dc.sponsorship.butantanCanada Foundation for Innovation¦¦31059pt_BR
dc.sponsorship.butantanCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)¦¦pt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.description.dbindexedYespt_BR
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