Slow translocon gating causes cytosolic exposure of transmembrane and lumenal domains during membrane protein integration
Biochemistry & Molecular Pharmacology
Graduate School of Biomedical Sciences; Department of Biochemistry and Molecular Pharmacology
Medical Subject Headings
Calcium-Binding Proteins; Cells, Cultured; Cytosol; Intracellular Membranes; Membrane Glycoproteins; Membrane Proteins; Models, Molecular; Permeability; Protein Folding; Protein Sorting Signals; Protein Transport; Receptors, Cytoplasmic and Nuclear; Receptors, Peptide; Saccharomyces cerevisiae Proteins; Translocation, Genetic; Ubiquitin; beta-Fructofuranosidase
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.
Rights and Permissions
Citation: Nat Struct Mol Biol. 2006 Oct;13(10):930-6. Epub 2006 Sep 17. Link to article on publisher's site
DOI of Published Version
Nature structural and molecular biology
Cheng, Zhiliang and Gilmore, Reid, "Slow translocon gating causes cytosolic exposure of transmembrane and lumenal domains during membrane protein integration" (2006). GSBS Student Publications. 204.