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dc.contributor.authorMujika, J.I.
dc.contributor.authorEscribano, B.
dc.contributor.authorAkhmatskaya, E. 
dc.contributor.authorUgalde, J.M.
dc.contributor.authorLopez, X.
dc.date.accessioned2017-02-21T08:16:48Z
dc.date.available2017-02-21T08:16:48Z
dc.date.issued2012-12-31
dc.identifier.issn0006-2960
dc.identifier.urihttp://hdl.handle.net/20.500.11824/406
dc.description.abstractSerum transferrin (sTf) carries iron in blood serum and delivers it into cells by receptor-mediated endocytosis. The protein can also bind other metals, including aluminum. The crystal structures of the metal-free and metal-loaded protein indicate that the metal release process involves an opening of the protein. In this process, Lys206 and Lys296 lying in the proximity of each other form the dilysine pair or, so-called, dilysine trigger. It was suggested that the conformational change takes place due to variations of the protonation state of the dilysine trigger at the acidic endosomal pH. In 2003, Rinaldo and Field (Biophys. J. 85, 3485-3501) proposed that the dilysine trigger alone can not explain the opening and that the protonation of Tyr188 is required to prompt the conformational change. However, no evidence was supplied to support this hypothesis. Here, we present several 60 ns molecular dynamics simulations considering various protonation states to investigate the complexes formed by sTf with Fe(III) and Al(III). The calculations demonstrate that only in those systems where Tyr188 has been protonated does the protein undergo the conformational change and that the dilysine trigger alone does not lead to the opening. The simulations also indicate that the metal release process is a stepwise mechanism, where the hinge-bending motion is followed by the hinge-twisting step. Therefore, the study demonstrates for the first time that the protonation of Tyr188 is required for the release of metal from the metal loaded sTf and provides valuable information about the whole process.
dc.formatapplication/pdf
dc.language.isoengen_US
dc.rightsReconocimiento-NoComercial-CompartirIgual 3.0 Españaen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/es/en_US
dc.titleMolecular dynamics simulations of iron- and aluminum-loaded serum transferrin: Protonation of tyr188 is necessary to prompt metal release
dc.typeinfo:eu-repo/semantics/articleen_US
dc.identifier.doi10.1021/bi300584p
dc.relation.publisherversionhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84865752254&doi=10.1021%2fbi300584p&partnerID=40&md5=6c34072f82a1f7116fc04d0b9f85f884
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessen_US
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersionen_US
dc.journal.titleBiochemistryen_US


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