Slow translocon gating causes cytosolic exposure of transmembrane and lumenal domains during membrane protein integration
Graduate School of Biomedical Sciences; Department of Biochemistry and Molecular Pharmacology
Life Sciences | Medicine and Health Sciences
Integral membrane proteins are cotranslationally inserted into the endoplasmic reticulum via the protein translocation channel, or translocon, which mediates the transport of lumenal domains, retention of cytosolic domains and integration of transmembrane spans into the phospholipid bilayer. Upon translocon binding, transmembrane spans interact with a lateral gate, which regulates access to membrane phospholipids, and a lumenal gate, which controls the translocation of soluble domains. We analyzed the in vivo kinetics of integration of model membrane proteins in Saccharomyces cerevisiae using ubiquitin translocation assay reporters. Our findings indicate that the conformational changes in the translocon that permit opening of the lumenal and lateral channel gates occur less rapidly than elongation of the nascent polypeptide. Transmembrane spans and lumenal domains are therefore exposed to the cytosol during integration of a polytopic membrane protein, which may pose a challenge to the fidelity of membrane protein integration.
DOI of Published Version
Nat Struct Mol Biol. 2006 Oct;13(10):930-6. Epub 2006 Sep 17. Link to article on publisher's site
Nature structural and molecular biology
Cheng Z, Gilmore R. (2006). Slow translocon gating causes cytosolic exposure of transmembrane and lumenal domains during membrane protein integration. Morningside Graduate School of Biomedical Sciences Student Publications. https://doi.org/10.1038/nsmb1146. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/204