Hydrophobicity, rather than secondary structure, is essential for the SRP dependent targeting of GPR35 to the ER membrane

Cherry, J. K. and Woolhead, C. A. (2019) Hydrophobicity, rather than secondary structure, is essential for the SRP dependent targeting of GPR35 to the ER membrane. Journal of Bioenergetics and Biomembranes, 51(2), pp. 137-150. (doi:10.1007/s10863-019-9785-0) (PMID:30706279) (PMCID:PMC6439181)

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Abstract

The folding and targeting of hydrophobic transmembrane domains poses a major challenge to the cell. Several membrane proteins have been shown to gain some degree of secondary structure within the ribosome tunnel and to retain this conformation throughout maturation. However, there is little information on one of the largest classes of eukaryotic membrane proteins; the G protein-coupled receptors (GPCRs). In this study we show that the signal anchor domain of GPR35 remains in an extended conformation whilst exiting the ribosome tunnel, the polypeptide chain then forms interactions with components of the SRP targeting pathway, and the Sec61 translocon, resulting in a compacted conformation prior to integration into the ER membrane. We conclude that transmembrane structure is most likely adopted after the domain leaves the ribosome tunnel and that the interaction of the signal anchor with SRP is dependent on the native levels of hydrophobicity within the first transmembrane domain. Therefore, we propose a mechanism by which the first transmembrane domains of multi-spanning membrane proteins adopt compacted structures following SRP targeting but before insertion into the ER membrane.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Woolhead, Professor Cheryl
Authors: Cherry, J. K., and Woolhead, C. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Journal of Bioenergetics and Biomembranes
Publisher:Springer
ISSN:0145-479X
ISSN (Online):1573-6881
Published Online:31 January 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Journal of Bioenergetics and Biomembranes 51(2):137-150
Publisher Policy:Reproduced under a Creative Commons License

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