Biological insertion of computationally designed short transmembrane segments

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  • dc.contributor.author Baeza Delgado, Carlosca
  • dc.contributor.author von Heijne, Gunnarca
  • dc.contributor.author Martí Renom, Marc A.ca
  • dc.contributor.author Mingarro, Ismaelca
  • dc.date.accessioned 2016-06-02T14:04:37Z
  • dc.date.available 2016-06-02T14:04:37Z
  • dc.date.issued 2016
  • dc.description.abstract The great majority of helical membrane proteins are inserted co-translationally into the ER membrane through a continuous ribosome-translocon channel. The efficiency of membrane insertion depends on transmembrane (TM) helix amino acid composition, the helix length and the position of the amino acids within the helix. In this work, we conducted a computational analysis of the composition and location of amino acids in transmembrane helices found in membrane proteins of known structure to obtain an extensive set of designed polypeptide segments with naturally occurring amino acid distributions. Then, using an in vitro translation system in the presence of biological membranes, we experimentally validated our predictions by analyzing its membrane integration capacity. Coupled with known strategies to control membrane protein topology, these findings may pave the way to de novo membrane protein design.ca
  • dc.description.sponsorship This work was supported by grants BFU2012-39482 to I.M. and BFU2010-19310/BMC and BFU2013-47736-P to M.A.M.-R. from the Spanish Ministry of Economy and Competitiveness (MINECO, co-financed by European Regional Development Fund), PROMETEOII/2014/061 from the Generalitat Valenciana to I.M., and by grants from the Swedish Foundation for Strategic Research, the European Research Council (ERC-2008-AdG 232648), the Swedish Cancer Foundation, the Swedish Research Council, and the Knut and Alice Wallenberg Foundation to GvH. C.B.-D. was recipient of a predoctoral FPI fellowship and an FPI short-staying grant from the MINECO to visit the laboratory of G.v.H.
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Baeza-Delgado C, von Heijne G, Marti-Renom MA, Mingarro I. Biological insertion of computationally designed short transmembrane segments. Scientific Reports. 2016; 6: 23397. DOI 10.1038/srep23397ca
  • dc.identifier.doi http://dx.doi.org/10.1038/srep23397
  • dc.identifier.issn 2045-2322
  • dc.identifier.uri http://hdl.handle.net/10230/26804
  • dc.language.iso engca
  • dc.publisher Nature Publishing Groupca
  • dc.relation.ispartof Scientific Reports. 2016; 6: 23397
  • dc.rights © Nature Publishing Group. http://www.nature.com/articles/srep23397/nThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.ca
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/ca
  • dc.subject.other Proteïnes de membranaca
  • dc.title Biological insertion of computationally designed short transmembrane segmentsca
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersionca