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dc.contributor.authorBustad, Helene J.en_US
dc.contributor.authorSkjærven, Larsen_US
dc.contributor.authorYing, Mingen_US
dc.contributor.authorHalskau, Øyvinden_US
dc.contributor.authorBaumann, Anneen_US
dc.contributor.authorRodriguez-Larrea, Daviden_US
dc.contributor.authorCostas, Miguelen_US
dc.contributor.authorUnderhaug, Jarlen_US
dc.contributor.authorSanchez-Ruiz, Jose M.en_US
dc.contributor.authorMartinez, Auroraen_US
dc.PublishedPLoS One 7(11): e49671eng
dc.description.abstractMammalian 14-3-3 protein scaffolds include seven conserved isoforms that bind numerous phosphorylated protein partners and regulate many cellular processes. Some 14-3-3-isoforms, notably γ, have elevated affinity for membranes, which might contribute to modulate the subcellular localization of the partners and substantiate the importance of investigating molecular mechanisms of membrane interaction. By applying surface plasmon resonance we here show that the binding to phospholipid bilayers is stimulated when 14-3-3γ is complexed with its partner, a peptide corresponding to the Ser19-phosphorylated N-terminal region of tyrosine hydroxylase. Moreover, membrane interaction is dependent on salts of kosmotropic ions, which also stabilize 14-3-3γ. Electrostatic analysis of available crystal structures of γ and of the non-membrane-binding ζ-isoform, complemented with molecular dynamics simulations, indicate that the electrostatic potential distribution of phosphopeptide-bound 14-3-3γ is optimal for interaction with the membrane through amphipathic helices at the N-terminal dimerization region. In addition, His158, and especially His195, both specific to 14-3-3γ and located at the convex lateral side, appeared to be pivotal for the ligand induced membrane interaction, as corroborated by site-directed mutagenesis. The participation of these histidine residues might be associated to their increased protonation upon membrane binding. Overall, these results reveal membrane-targeting motifs and give insights on mechanisms that furnish the 14-3-3γ scaffold with the capacity for tuned shuffling from soluble to membrane-bound states.en_US
dc.publisherPublic Library of Scienceeng
dc.rightsAttribution CC BYeng
dc.titleThe Peripheral Binding of 14-3-3γ to Membranes Involves Isoform-Specific Histidine Residuesen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2012 Bustad et al.

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