The expanding role of the ER translocon in membrane protein folding.
Eukaryotic polytopic membrane proteins are cotranslationally inserted into the ER membrane by a multisubunit protein-conducting channel called the Sec61 translocon. Although most major translocon components have been identified and reconstituted, their stoichiometry and functional organization remain unknown. This has led to speculative and sometimes conflicting models describing how multiple transmembrane (TM) segments might be oriented and integrated during nascent polytopic protein biogenesis. Kida et al. (see p. 1441 of this issue) shed new insight into this area by demonstrating that functional translocons exhibit a remarkable flexibility by simultaneously accommodating at least two hydrophilic translocating peptides that are separated by multiple hydrophobic TMs. These surprising findings support an expanded role for the translocon in membrane protein biogenesis and require reassessment of current views based on a single small functional pore.
Skach
William R
WR
Department of Biochemistry and Molecular Biology, Oregon Health & Sciences University, Portland, OR 97239, USA. skachw@ohsu.edu
D000818:Animals; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism* / Q000648:ultrastructure; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding; D021381:Protein Transport / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism; D018000:Receptors, Peptide / Q000737:chemistry / Q000378:metabolism; D000069816:SEC Translocation Channels
D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D008563:Membrane Lipids; D008565:Membrane Proteins; D010455:Peptides; D018160:Receptors, Cytoplasmic and Nuclear; D018000:Receptors, Peptide; D000069816:SEC Translocation Channels; C066973:signal sequence receptor