Membrane Insertion of Marginally Hydrophobic Transmembrane Helices Depends on Sequence Context
2010 (English)In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 396, no 1, 221-229 p.Article in journal (Refereed) Published
In mammalian cells, most integral membrane proteins are initially inserted into the endoplasmic reticulum membrane by the so-called Sec61 translocon. However, recent predictions suggest that many transmembrane helices (TMHs) in multispanning membrane proteins are not sufficiently hydrophobic to be recognized as such by the translocon. In this study, we have screened 16 marginally hydrophobic TMHs from membrane proteins of known three-dimensional structure. Indeed, most of these TMHs do not insert efficiently into the endoplasmic reticulum membrane by themselves. To test if loops or TMHs immediately upstream or downstream of a marginally hydrophobic helix might influence the insertion efficiency, insertion of marginally hydrophobic helices was also studied in the presence of their neighboring loops and helices. The results show that flanking loops and nearest-neighbor TMHs are sufficient to ensure the insertion of many marginally hydrophobic helices. However, for at least two of the marginally hydrophobic helices, the local interactions are not enough, indicating that post-insertional rearrangements are involved in the folding of these proteins.
Place, publisher, year, edition, pages
2010. Vol. 396, no 1, 221-229 p.
marginally hydrophobic helix, membrane protein, topology, hydrophobicity
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject Biochemistry with Emphasis on Theoretical Chemistry
IdentifiersURN: urn:nbn:se:su:diva-33926DOI: 10.1016/j.jmb.2009.11.036ISI: 000274766500018PubMedID: 19931281OAI: oai:DiVA.org:su-33926DiVA: diva2:283817
FunderEU, FP7, Seventh Framework Programme, 503265; 512092; 201924Swedish Research CouncilSwedish Foundation for Strategic Research
authorCount :122009-12-302009-12-302016-02-23Bibliographically approved