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 r...

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Bibliographic Details
Published in:Journal of molecular biology 2010-02, Vol.396 (1), p.221-229
Main Authors: Hedin, 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
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Biochemistry
Biochemistry with Emphasis on Theoretical Chemistry
Biokemi
biokemi, inriktning teoretisk kemi
Biological Assay
Cell Membrane - metabolism
Chemistry
Humans
Hydrophobic and Hydrophilic Interactions
hydrophobicity
Kemi
marginally hydrophobic helix
MEDICIN
MEDICINE
membrane protein
Protein Structure, Secondary
Proteins - chemistry
Proteins - metabolism
Thermodynamics
topology
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Summary: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.
ISSN:0022-2836
1089-8638
1089-8638
DOI:10.1016/j.jmb.2009.11.036