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Enthalpic and entropic contributions mediate the role of disulfide bonds on the conformational stability of Interleukin-4

2006Journal article Restricted access
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dc.contributor.authorVaz, Daniela C.
dc.contributor.authorRodrigues, J. Rui
dc.contributor.authorSebald, Walter
dc.contributor.authorDobson, Christopher M.
dc.contributor.authorBrito, Rui M. M.
dc.date.accessioned2019-10-30T10:17:40Z
dc.date.available2019-10-30T10:17:40Z
dc.date.issued2006
dc.date.updated2019-10-28T11:40:50Z
dc.description.abstractThe role of disulfide bridges in the structure, stability, and folding pathways of proteins has been the subject of wide interest in the fields of protein design and engineering. However, the relative importance of entropic and enthalpic contributions for the stabilization of proteins provided by disulfides is not always clear. Here, we perform a detailed analysis of the role of disulfidesin the conformational stability of human Interleukin-4 (IL4), a four-helix bundle protein. In order to evaluate the contribution of two out of the three disulfides to the structure and stability of IL4, two IL4 mutants, C3T-IL4 and C24T-IL4, were used. NMR and ANS binding experiments were compatible with altered dynamics and an increase of the nonpolar solventaccessible surface area of the folded state of the mutant proteins. Chemical and thermal unfolding experiments followed by fluorescence and circular dichroism revealed that both mutant proteins have lower conformational stability than the wild-type protein. Transition temperatures of unfolding decreased 14C for C3T-IL4 and 10C for C24T-IL4, when compared toWT-IL4, and the conformational stability, at 25C, decreased 4.9 kcal/mol for C3T-IL4 and 3.2 kcal/mol for C24T-IL4. Interestingly, both the enthalpy and the entropy of unfolding, at the transition temperature, decreased in the mutant proteins. Moreover, a smaller change in heat capacity of unfolding was also observed for the mutants. Thus, disulfide bridges in IL4 play a critical role in maintaining the thermodynamic stability and core packing of the helix bundle.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1110/ps.051593306
dc.identifier.other2-s2.0-29344441722
dc.identifier.slugcv-prod-179874
dc.identifier.urihttp://hdl.handle.net/10400.8/4260
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationPOCTI/BIO/35685/ 2000pt_PT
dc.relationESTRUTURA, ESTABILIDADE CONFORMACIONAL E FOLDING EM VARIANTES DAS PROTEÍNAS TRANSTIRRETINA HUMANA E INTERLEUCINA-4 HUMANA
dc.relation.ispartofProtein Scienceen_US
dc.subjectInterleukin-4pt_PT
dc.subjectFour-helix bundlept_PT
dc.subjectConformational stabilitypt_PT
dc.subjectDisulfide bridgespt_PT
dc.subjectUreapt_PT
dc.subjectThermal unfoldingpt_PT
dc.subjectEnthalpypt_PT
dc.subjectEntropypt_PT
dc.titleEnthalpic and entropic contributions mediate the role of disulfide bonds on the conformational stability of Interleukin-4pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleESTRUTURA, ESTABILIDADE CONFORMACIONAL E FOLDING EM VARIANTES DAS PROTEÍNAS TRANSTIRRETINA HUMANA E INTERLEUCINA-4 HUMANA
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F3279%2F2000/PT
oaire.citation.endPage44pt_PT
oaire.citation.startPage33pt_PT
oaire.citation.titleProtein Sciencept_PT
oaire.citation.volume15pt_PT
person.familyNameBarroso de Moura Cipreste Vaz
person.givenNameDaniela
person.identifier.ciencia-id801A-7761-328C
person.identifier.orcid0000-0001-7562-4676
person.identifier.ridR-5243-2017
person.identifier.scopus-author-id6602838931
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.cv.cienciaid801A-7761-328C | Daniela Maria Barroso de Moura Cipreste Vaz
rcaap.rightsclosedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication518f12af-3297-4334-b00b-c06e17b2cf27
relation.isAuthorOfPublication.latestForDiscovery518f12af-3297-4334-b00b-c06e17b2cf27
relation.isProjectOfPublicationeaf6e959-2d2e-4a7e-89a4-37f2d65b69cd
relation.isProjectOfPublication.latestForDiscoveryeaf6e959-2d2e-4a7e-89a4-37f2d65b69cd

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