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

Lookup NU author(s): Dr Jon Cherry

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Abstract

© 2019, The Author(s). 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.

Publication metadata

Author(s): Cherry JK, Woolhead CA

Publication type: Article

Publication status: Published

Journal: Journal of Bioenergetics and Biomembranes

Year: 2019

Volume: 51

Pages: 137-150

Online publication date: 31/01/2019

Acceptance date: 15/01/2019

ISSN (print): 0145-479X

ISSN (electronic): 1573-6881

Publisher: Springer

URL: https://doi.org/10.1007/s10863-019-9785-0

DOI: 10.1007/s10863-019-9785-0

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