Dynamin-2 R465W mutation induces long range perturbation in highly ordered oligomeric structures

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dc.contributor.authorHinostroza F.
dc.contributor.authorNeely A.
dc.contributor.authorAraya-Duran I.
dc.contributor.authorMarabolí V.
dc.contributor.authorCanan J.
dc.contributor.authorRojas M.
dc.contributor.authorAguayo D.
dc.contributor.authorLatorre R.
dc.contributor.authorGonzález-Nilo F.D.
dc.contributor.authorCárdenas A.M.
dc.date.accessioned2021-09-06T21:26:34Z
dc.date.available2021-09-06T21:26:34Z
dc.date.issued2020-12
dc.description.abstractHigh order oligomers are crucial for normal cell physiology, and protein function perturbed by missense mutations underlies several autosomal dominant diseases. Dynamin-2 is one of such protein forming helical oligomers that catalyze membrane fission. Mutations in this protein, where R465W is the most frequent, cause dominant centronuclear myopathy, but the molecular mechanisms underpinning the functional modifications remain to be investigated. To unveil the structural impact of this mutation in dynamin-2, we used full-atom molecular dynamics simulations and coarse-grained models and built dimers and helices of wild-type (WT) monomers, mutant monomers, or both WT and mutant monomers combined. Our results show that the mutation R465W causes changes in the interactions with neighbor amino acids that propagate through the oligomer. These new interactions perturb the contact between monomers and favor an extended conformation of the bundle signaling element (BSE), a dynamin region that transmits the conformational changes from the GTPase domain to the rest of the protein. This extended configuration of the BSE that is only relevant in the helices illustrates how a small change in the microenvironment surrounding a single residue can propagate through the oligomer structures of dynamin explaining how dominance emerges in large protein complexes. © 2020, The Author(s).es
dc.description.sponsorshipIndexación Scopuses
dc.description.urihttps://www-nature-com.recursosbiblioteca.unab.cl/articles/s41598-020-75216-0
dc.identifier.citationScientific Reports, Volume 10, Issue 11 December 2020 Article number 18151es
dc.identifier.doi10.1038/s41598-020-75216-0
dc.identifier.issn20452322
dc.identifier.urihttp://repositorio.unab.cl/xmlui/handle/ria/20153
dc.language.isoeses
dc.publisherNature Researches
dc.subjectDynaminses
dc.subjectDynasorees
dc.subjectAmphiphysines
dc.titleDynamin-2 R465W mutation induces long range perturbation in highly ordered oligomeric structureses
dc.typeArtículoes
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