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 FieldValueLanguage
dc.contributorLaboratório Especial de Toxinologia Aplicada (LETA)pt_BR
dc.contributor.authorZelanis Apt_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.accessioned2020-07-09T21:25:07Z-
dc.date.available2020-07-09T21:25:07Z-
dc.date.issued2019-
dc.identifier.citationZA, 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 Jul;18(9):3419-3428. doi:10.1021/acs.jproteome.9b00325.pt_BR
dc.identifier.issn1535-3893-
dc.identifier.issn1535-3907-
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/2834-
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.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.format.extent3419-3428pt_BR
dc.languageengpt_BR
dc.publisherAmerican Chemical Societypt_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)¦¦Brasilpt_BR
dc.contributor.externalUniversity of British Columbia (UBC)¦¦Canadápt_BR
dc.publisher.cityWashingtonpt_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 Jul;18(9):3419-3428pt_BR
dc.publisher.countryUnited Statespt_BR
dc.contributor.butantanZelanis A|:Aluno|:Laboratório Especial de Toxinologia Aplicada (LETA)|:PrimeiroAutorpt_BR
dc.contributor.butantanSerrano, Solange Maria de Toledo|:Pesquisador:Docente Permanente PPGTOX|:Laboratório Especial de Toxinologia Aplicada (LETA)|:Autor de correspondênciapt_BR
dc.contributor.butantanOliveira, Ana Karina de|:Aluno|:Laboratório Especial de Toxinologia Aplicada (LETA)|:pt_BR
dc.contributor.butantanTashima, Alexandre Keiji|:Aluno|:Laboratório Especial de Toxinologia Aplicada (LETA)|:pt_BR
dc.sponsorship.butantanConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)¦¦308133/2015-3pt_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.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.subject.researchlineToxinologia estruturalpt_BR
item.openairetypeArticle-
item.fulltextCom Texto completo-
item.grantfulltextembargo_29990101-
crisitem.journal.journalissn#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.journal.journaleissn#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.dept#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.orcid#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.parentorg#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.parentorg#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.parentorg#PLACEHOLDER_PARENT_METADATA_VALUE#-
crisitem.author.parentorg#PLACEHOLDER_PARENT_METADATA_VALUE#-
Appears in Collections:Artigos de periódicos

Files in This Item:
File SizeFormat Existing users please Login
10.1021.acs.jproteome.9b00325.pdf1.65 MBAdobe PDFEmbargoed until January 1, 2999    Request a copy
Show simple item record

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.