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Membrane Insertion of Marginally Hydrophobic Transmembrane Helices Depends on Sequence Context

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. / <p>authorCount :12</p>

Identiferoai:union.ndltd.org:UPSALLA1/oai:DiVA.org:su-33926
Date January 2010
CreatorsHedin, Linnea E., Öjemalm, Karin, Bernsel, Andreas, Hennerdal, Aron, Illergård, Kristoffer, Enquist, Karl, Kauko, Anni, Cristobal, Susana, von Heijne, Gunnar, Lerch-Bader, Mirjam, Nilsson, Ingmarie, Elofsson, Arne
PublisherStockholms universitet, Institutionen för biokemi och biofysik, Stockholms universitet, Institutionen för biokemi och biofysik, Stockholms universitet, Institutionen för biokemi och biofysik, Stockholms universitet, Institutionen för biokemi och biofysik, Stockholms universitet, Institutionen för biokemi och biofysik, Stockholms universitet, Institutionen för biokemi och biofysik, Stockholms universitet, Institutionen för biokemi och biofysik, Stockholms universitet, Institutionen för biokemi och biofysik, Stockholms universitet, Institutionen för biokemi och biofysik, Stockholms universitet, Institutionen för biokemi och biofysik, Stockholms universitet, Institutionen för biokemi och biofysik, Stockholms universitet, Institutionen för biokemi och biofysik
Source SetsDiVA Archive at Upsalla University
LanguageEnglish
Detected LanguageEnglish
TypeArticle in journal, info:eu-repo/semantics/article, text
Formatapplication/pdf
Rightsinfo:eu-repo/semantics/openAccess
RelationJournal of Molecular Biology, 0022-2836, 2010, 396:1, s. 221-229, info:eu-repo/grantAgreement/EC/FP7/503265; 512092; 201924

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