title: Insertion of short transmembrane helices by the Sec61 translocon.
abstract: The insertion efficiency of transmembrane (TM) helices by the Sec61 translocon depends on helix amino acid composition, the positions of the amino acids within the helix, and helix length. We have used an in vitro expression system to examine systematically the insertion efficiency of short polyleucine segments (L(n), n = 4 ... 12) flanked at either end by 4-residue sequences of the form XXPX-L(n)-XPXX with X = G, N, D, or K. Except for X = K, insertion efficiency (p) is <10% for n < 8, but rises steeply to 100% for n = 12. For X = K, p is already close to 100% for n = 10. A similar pattern is observed for synthetic peptides incorporated into oriented phospholipid bilayer arrays, consistent with the idea that recognition of TM segments by the translocon critically involves physical partitioning of nascent peptide chains into the lipid bilayer. Molecular dynamics simulations suggest that insertion efficiency is determined primarily by the energetic cost of distorting the bilayer in the vicinity of the TM helix. Very short lysine-flanked leucine segments can reduce the energetic cost by extensive hydrogen bonding with water and lipid phosphate groups (snorkeling) and by partial unfolding.
authors: Department of Chemistry and the Center for Biomembrane Systems, University of California, Irvine, CA 92697-2025, USA.
authors: Simon
authors: S
authors: Jaud
authors: Mónica
authors: M
authors: Fernández-Vidal
authors: Ingmarie
authors: I
authors: Nilsson
authors: Nadja M
authors: NM
authors: Meindl-Beinker
authors: Nadja C
authors: NC
authors: Hübner
authors: Douglas J
authors: DJ
authors: Tobias
authors: Gunnar
authors: G
authors: von Heijne
authors: Stephen H
authors: SH
authors: White
mesh_terms: D003198:Computer Simulation; D006860:Hydrogen Bonding; D008051:Lipid Bilayers / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D010455:Peptides / Q000378:metabolism*; D000069816:SEC Translocation Channels
chemical_list: D008051:Lipid Bilayers; D008565:Membrane Proteins; D010455:Peptides; D000069816:SEC Translocation Channels; C027819:polyleucine