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)

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 > School of Molecular Biosciences
• 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