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dc.contributor.authorGiganti, David
dc.contributor.authorYan, Kevin
dc.contributor.authorBadilla, Carmen L.
dc.contributor.authorFernandez, Julio M.
dc.contributor.authorAlegre-Cebollada, Jorge 
dc.date.accessioned2018-11-22T08:10:54Z
dc.date.available2018-11-22T08:10:54Z
dc.date.issued2018
dc.identifierISI:000419949200012
dc.identifier.citationNat Commun. 2018; 9(1):185
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6695
dc.description.abstractThe response of titin to mechanical forces is a major determinant of the function of the heart. When placed under a pulling force, the unstructured regions of titin uncoil while its immunoglobulin (Ig) domains unfold and extend. Using single-molecule atomic force microscopy, we show that disulfide isomerization reactions within Ig domains enable a third mechanism of titin elasticity. Oxidation of Ig domains leads to non-canonical disulfide bonds that stiffen titin while enabling force-triggered isomerization reactions to more extended states of the domains. Using sequence and structural analyses, we show that 21\% of titin's I-band Ig domains contain a conserved cysteine triad that can engage in disulfide isomerization reactions. We propose that imbalance of the redox status of myocytes can have immediate consequences for the mechanical properties of the sarcomere via alterations of the oxidation state of titin domains.
dc.description.sponsorshipJ.M.F. acknowledges support from NSF (DBI-1252857) and NIH (GM116122 and HL061228) grants. J.A.-C. acknowledges funding from the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) through grants BIO2014-54768-P and RYC-2014-16604. The CNIC is supported by MINECO and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). D.G. was a recipient of a Marie Sklodowska-Curie Individual Fellowship (656721). We thank Diego Rojas and Georgia Squyres for excellent technical support. We thank Elias Herrero-Galan (CNIC, Madrid) for critical reading of the manuscript.
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.isversionofPublisher's version
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleDisulfide isomerization reactions in titin immunoglobulin domains enable a mode of protein elasticity
dc.typeArtículo
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID29330363
dc.format.volume9
dc.identifier.doi10.1038/s41467-017-02528-7
dc.contributor.funderNational Science Foundation (United States)
dc.contributor.funderNational Institutes of Health (United States)
dc.contributor.funderMinisterio de Economía, Industria y Competitividad (España)
dc.contributor.funderFundación ProCNIC
dc.contributor.funderEuropean Commission
dc.description.peerreviewed
dc.relation.publisherversionhttps://doi.org/10.1038/s41467-017-02528-7
dc.identifier.journalNature Communications
dc.repisalud.orgCNICCNIC::Grupos de investigación::Mecánica molecular del sistema cardiovascular
dc.repisalud.institucionCNIC
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BIO2014-54768-Pes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/RYC-2014-16604es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/656721es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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