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The Positive Inside Rule Is Stronger When Followed by a Transmembrane Helix
Stockholm University, Sweden .
Stockholm University, Sweden; Swedish e-Science Research Center (SeRC), Stockholm, Sweden.
Stockholm University, Sweden .
Stockholm University, Sweden .
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2014 (English)In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 426, no 16, 2982-2991 p.Article in journal (Refereed) Published
Abstract [en]

The translocon recognizes transmembrane helices with sufficient level of hydrophobicity and inserts them into the membrane. However, sometimes less hydrophobic helices are also recognized. Positive inside rule, orientational preferences of and specific interactions with neighboring helices have been shown to aid in the recognition of these helices, at least in artificial systems. To better understand how the translocon inserts marginally hydrophobic helices, we studied three naturally occurring marginally hydrophobic helices, which were previously shown to require the subsequent helix for efficient translocon recognition. We find no evidence for specific interactions when we scan all residues in the subsequent helices. Instead, we identify arginines located at the N-terminal part of the subsequent helices that are crucial for the recognition of the marginally hydrophobic transmembrane helices, indicating that the positive inside rule is important. However, in two of the constructs, these arginines do not aid in the recognition without the rest of the subsequent helix; that is, the positive inside rule alone is not sufficient. Instead, the improved recognition of marginally hydrophobic helices can here be explained as follows: the positive inside rule provides an orientational preference of the subsequent helix, which in turn allows the marginally hydrophobic helix to be inserted; that is, the effect of the positive inside rule is stronger if positively charged residues are followed by a transmembrane helix. Such a mechanism obviously cannot aid C-terminal helices, and consequently, we find that the terminal helices in multi-spanning membrane proteins are more hydrophobic than internal helices.

Place, publisher, year, edition, pages
Elsevier, 2014. Vol. 426, no 16, 2982-2991 p.
Keyword [en]
marginally hydrophobic helices; translocon recognition; membrane proteins; positive inside rule; orientational preference
National Category
Clinical Medicine Biological Sciences
URN: urn:nbn:se:liu:diva-110273DOI: 10.1016/j.jmb.2014.06.002ISI: 000340327500007PubMedID: 24927974OAI: diva2:744052

Funding Agencies|Swedish Research Council [VR-NT 2009-5072, 2012-5046, VR-M 2010-3555]; Foundation for Strategic Research; Swedish E-Science Research Center; European Union [FP7-HEALTH-F4-2007-201924]; Swedish Foundation for Strategic Research; Science for Life Laboratory

Available from: 2014-09-05 Created: 2014-09-05 Last updated: 2015-03-24Bibliographically approved

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