Slow translocon gating causes cytosolic exposure of transmembrane and lumenal domains during membrane protein integration. 2006

Zhiliang Cheng, and Reid Gilmore
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605-2324, USA.

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.

UI MeSH Term Description Entries
D007425 Intracellular Membranes Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES. Membranes, Intracellular,Intracellular Membrane,Membrane, Intracellular
D008562 Membrane Glycoproteins Glycoproteins found on the membrane or surface of cells. Cell Surface Glycoproteins,Surface Glycoproteins,Cell Surface Glycoprotein,Membrane Glycoprotein,Surface Glycoprotein,Glycoprotein, Cell Surface,Glycoprotein, Membrane,Glycoprotein, Surface,Glycoproteins, Cell Surface,Glycoproteins, Membrane,Glycoproteins, Surface,Surface Glycoprotein, Cell,Surface Glycoproteins, Cell
D008565 Membrane Proteins Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D010539 Permeability Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions. Permeabilities
D002135 Calcium-Binding Proteins Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS. Calcium Binding Protein,Calcium-Binding Protein,Calcium Binding Proteins,Binding Protein, Calcium,Binding Proteins, Calcium,Protein, Calcium Binding,Protein, Calcium-Binding
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003600 Cytosol Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components. Cytosols
D000069816 SEC Translocation Channels Universally conserved multiprotein complexes that form the protein transport channel of the general secretory (SEC) pathway. The SEC translocase is present in all bacteria, archaea, and eukaryotes. It is in the ENDOPLASMIC RETICULUM membrane of eukaryotic cells, in the THYLAKOID MEMBRANE in CHLOROPLASTS and in some protozoa in the INNER MITOCHONDRIAL MEMBRANE. SEC Translocation Channel,SEC Translocon,SEC61 Translocation Channel,Sec Protein Translocation System,SecYEG Protein,SecYEG Translocation Channel,SEC Complexes,SEC Translocase,SEC Translocons,SEC61 Protein,SEC61 Proteins,SEC61 Translocase,SEC61 Translocation Channels,SEC61 Translocon,Sec Protein Translocation Systems,Sec61 Complex,Sec61 Protein Translocation System,SecY Translocase,SecYEG Complex,SecYEG Complexes,SecYEG Protein Translocation System,SecYEG Proteins,SecYEG Translocation Channels,SecYEG Translocon,Channel, SEC Translocation,Channel, SEC61 Translocation,Channel, SecYEG Translocation,Channels, SEC Translocation,Channels, SEC61 Translocation,Channels, SecYEG Translocation,Complex, Sec61,Complex, SecYEG,Complexes, SEC,Complexes, SecYEG,Protein, SEC61,Protein, SecYEG,Proteins, SEC61,Proteins, SecYEG,Translocase, SEC,Translocase, SEC61,Translocase, SecY,Translocation Channel, SEC,Translocation Channel, SEC61,Translocation Channel, SecYEG,Translocation Channels, SEC,Translocation Channels, SEC61,Translocation Channels, SecYEG,Translocon, SEC,Translocon, SEC61,Translocon, SecYEG,Translocons, SEC
D014178 Translocation, Genetic A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome. Chromosomal Translocation,Translocation, Chromosomal,Chromosomal Translocations,Genetic Translocation,Genetic Translocations,Translocations, Chromosomal,Translocations, Genetic

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