title: Reorientation of the first signal-anchor sequence during potassium channel biogenesis at the Sec61 complex.
abstract: The majority of the polytopic proteins that are synthesized at the ER (endoplasmic reticulum) are integrated co-translationally via the Sec61 translocon, which provides lateral access for their hydrophobic TMs (transmembrane regions) to the phospholipid bilayer. A prolonged association between TMs of the potassium channel subunit, TASK-1 [TWIK (tandem-pore weak inwardly rectifying potassium channel)-related acid-sensitive potassium channel 1], and the Sec61 complex suggests that the ER translocon co-ordinates the folding/assembly of the TMs present in the nascent chain. The N-terminus of both TASK-1 and Kcv (potassium channel protein of chlorella virus), another potassium channel subunit of viral origin, has access to the N-glycosylation machinery located in the ER lumen, indicating that the Sec61 complex can accommodate multiple arrangements/orientations of TMs within the nascent chain, both in vitro and in vivo. Hence the ER translocon can provide the ribosome-bound nascent chain with a dynamic environment in which it can explore a range of different conformations en route to its correct transmembrane topology and final native structure.
authors.affiliation: *Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, U.K.
authors.forename: Helen R
authors.initials: HR
authors.lastname: Watson
authors.forename: Lydia
authors.initials: L
authors.lastname: Wunderley
authors.forename: Tereza
authors.initials: T
authors.lastname: Andreou
authors.forename: Jim
authors.initials: J
authors.lastname: Warwicker
authors.forename: Stephen
authors.initials: S
authors.lastname: High
mesh_terms: D004721:Endoplasmic Reticulum / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000096:biosynthesis* / Q000737:chemistry; D021382:Protein Sorting Signals; D017433:Protein Structure, Secondary; D000069816:SEC Translocation Channels
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D024683:Potassium Channels, Tandem Pore Domain; D021382:Protein Sorting Signals; D000069816:SEC Translocation Channels; C420132:potassium channel subfamily K member 3