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dc.contributor.authorJurado, Samuel
dc.contributor.authorCano-Muñoz, Mario
dc.contributor.authorPolo-Megías, Daniel
dc.contributor.authorMorel, Bertrand
dc.contributor.authorConejero Lara, Francisco 
dc.date.accessioned2021-03-09T12:31:40Z
dc.date.available2021-03-09T12:31:40Z
dc.date.issued2020
dc.identifier.citationJurado, S., Cano-Muñoz, M., Polo-Megías, D., Conejero-Lara, F., & Morel, B. (2020). Thermodynamic dissection of the interface between HIV-1 gp41 heptad repeats reveals cooperative interactions and allosteric effects. Archives of biochemistry and biophysics, 688, 108401.es_ES
dc.identifier.urihttp://hdl.handle.net/10481/67028
dc.description.abstractHIV-1 glycoprotein 41 (gp41) mediates fusion between virus and target cells by folding into a fusion active state, in which the C-terminal heptad repeat (CHR) regions associate externally to the N-terminal heptad repeat (NHR) trimer and form a very stable six-helix bundle coiled-coil structure. Therefore, interfering with the NHR-CHR interaction of gp41 is a promising therapeutic approach against HIV-1. However, a full understanding of the molecular and mechanistic details of this interaction is still incomplete. Here, we use single-chain, chimeric proteins (named covNHR) that reproduce accurately the CHR-NHR interactions to analyze the binding thermodynamics of several peptides with different length from the CHR region. The results indicate that cooperative binding involving two or more pockets of the NHR groove is necessary to obtain relevant affinities and that the binding energy is broadly distributed along the interface, underlining a crucial role of a middle pocket to achieve tight binding. In contrast, targeting only the deep hydrophobic pocket is insufficient to achieve significant affinity. Moreover, calorimetry experiments in combination with limited proteolysis performed using a mutant with occluded binding in the N-terminal pocket reveal the existence of an allosteric communication between the different regions. This study is the first detailed thermodynamic dissection of the NHR-CHR interaction in gp41 and contributes therefore to a better understanding of HIV fusion. These results are relevant for the development of potential fusion inhibitors.es_ES
dc.description.sponsorshipGrant BIO2016-76640-R from the Spanish Ministry of Economy and Competitiveness and by the European Fund for Research and Development from the European Union.es_ES
dc.description.sponsorshipDepartamento de Química Física, Facultad de Ciencias, Universidad de Granada. Grupo FQM-171 "Biofísica y Biotecnología Molecular"es_ES
dc.language.isoenges_ES
dc.publisherELSEVIERes_ES
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 España*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/*
dc.subjectCalorimetry es_ES
dc.subjectPeptides es_ES
dc.subjectBinding affinityes_ES
dc.subjectCoiled-coiles_ES
dc.subjectFusion inhibitorses_ES
dc.titleThermodynamic dissection of the interface between HIV-1 gp41 heptad repeats reveals cooperative interactions and allosteric effectses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.accessRightsinfo:eu-repo/semantics/embargoedAccesses_ES
dc.identifier.doi10.1016/j.abb.2020.108401
dc.type.hasVersioninfo:eu-repo/semantics/submittedVersiones_ES


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Atribución-NoComercial-SinDerivadas 3.0 España
Except where otherwise noted, this item's license is described as Atribución-NoComercial-SinDerivadas 3.0 España