
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
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor | (LETA) Lab. Toxinologia Aplicada | pt_BR |
dc.contributor | (CeTICS) Centro de Toxinas, Resposta-imune e Sinalização Celular | pt_BR |
dc.contributor.author | Pereira, André Zelanis Palitot | pt_BR |
dc.contributor.author | Oliveira, Ana Karina de | pt_BR |
dc.contributor.author | Prudova, Anna | pt_BR |
dc.contributor.author | Huesgen, Pitter F. | pt_BR |
dc.contributor.author | Tashima, Alexandre Keiji | pt_BR |
dc.contributor.author | Kizhakkedathu, Jayachandran | pt_BR |
dc.contributor.author | Overall, Christopher M. | pt_BR |
dc.contributor.author | Serrano, Solange Maria de Toledo | pt_BR |
dc.date.accessioned | 2020-08-14T19:55:42Z | - |
dc.date.available | 2020-08-14T19:55:42Z | - |
dc.date.issued | 2019 | pt_BR |
dc.identifier.citation | Pereira 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.uri | https://repositorio.butantan.gov.br/handle/butantan/3133 | - |
dc.description.abstract | Snakebite 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 Paulo | pt_BR |
dc.description.sponsorship | (CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico | pt_BR |
dc.description.sponsorship | (CRC) Canada Research Chairs | pt_BR |
dc.description.sponsorship | (MSFHR) Michael Smith Foundation for Health Research | pt_BR |
dc.description.sponsorship | (CFI) Canada Foundation for Innovation | pt_BR |
dc.description.sponsorship | (CIHR) Canadian Institutes of Health Research | pt_BR |
dc.format.extent | 3419-3428 | pt_BR |
dc.language.iso | English | pt_BR |
dc.relation.ispartof | Journal of Proteome Research | pt_BR |
dc.rights | Restricted access | pt_BR |
dc.title | 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 | pt_BR |
dc.type | Article | pt_BR |
dc.identifier.doi | 10.1021/acs.jproteome.9b00325 | pt_BR |
dc.identifier.url | https://doi.org/10.1021/acs.jproteome.9b00325 | pt_BR |
dc.contributor.external | (UNIFESP) Universidade Federal de São Paulo | pt_BR |
dc.contributor.external | (UBC) University of British Columbia | pt_BR |
dc.identifier.citationvolume | 18 | pt_BR |
dc.identifier.citationissue | 9 | pt_BR |
dc.subject.keyword | degradome | pt_BR |
dc.subject.keyword | snake venom metalloprotease | pt_BR |
dc.subject.keyword | HF3 | pt_BR |
dc.subject.keyword | proteomic identification of cleavage sites | pt_BR |
dc.subject.keyword | PICS | pt_BR |
dc.subject.keyword | terminal amine isotopic labeling of substrates | pt_BR |
dc.subject.keyword | TAILS | pt_BR |
dc.relation.ispartofabbreviated | J Proteome Res | pt_BR |
dc.identifier.citationabnt | v. 18, n. 9, p. 3419-3428, jul. 2019 | pt_BR |
dc.identifier.citationvancouver | 2019 July;18(9):3419-3428 | pt_BR |
dc.contributor.butantan | Pereira, André Zelanis Palitot|:Aluno|:(LETA) Lab. Toxinologia Aplicada:Centro de Toxinas, Resposta-imune e Sinalização Celular (CeTICS)|:PrimeiroAutor | pt_BR |
dc.contributor.butantan | Oliveira, Ana Karina de|:Aluno|:(LETA) Lab. Toxinologia Aplicada:Centro de Toxinas, Resposta-imune e Sinalização Celular (CeTICS) | pt_BR |
dc.contributor.butantan | Tashima, Alexandre Keiji|:Aluno|:(LETA) Lab. Toxinologia Aplicada:Centro de Toxinas, Resposta-imune e Sinalização Celular (CeTICS) | pt_BR |
dc.contributor.butantan | Serrano, Solange Maria de Toledo|:Pesquisador:Docente Permanente PPGTOX|:(LETA) Lab. Toxinologia Aplicada:Centro de Toxinas, Resposta-imune e Sinalização Celular (CeTICS)|:Autor de correspondência | pt_BR |
dc.sponsorship.butantan | Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2013/07467-1 | pt_BR |
dc.sponsorship.butantan | Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2011/23403-8 | pt_BR |
dc.sponsorship.butantan | Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2011/08514-8 | pt_BR |
dc.sponsorship.butantan | Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2010/17328-0 | pt_BR |
dc.sponsorship.butantan | Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)¦¦308133/2015-3) | pt_BR |
dc.sponsorship.butantan | Canada Research Chairs¦¦950-20-3877 | pt_BR |
dc.sponsorship.butantan | Canadian Institutes of Health Research (CIHR)¦¦FDN-148408 | pt_BR |
dc.sponsorship.butantan | Michael Smith Foundation for Health Research¦¦IN-NPG-0010 | pt_BR |
dc.sponsorship.butantan | Canada Foundation for Innovation¦¦31059 | pt_BR |
dc.sponsorship.butantan | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)¦¦ | pt_BR |
dc.identifier.bvscc | BR78.1 | pt_BR |
dc.identifier.bvsdb | IBProd | pt_BR |
dc.description.dbindexed | Yes | pt_BR |
item.fulltext | Com Texto completo | - |
item.languageiso639-1 | English | - |
item.openairetype | Article | - |
item.grantfulltext | embargo_29990101 | - |
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