Molecular code for transmembrane-helix recognition by the Sec61 translocon
Top Cited Papers
- 1 December 2007
- journal article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 450 (7172), 1026-1030
- https://doi.org/10.1038/nature06387
Abstract
Transmembrane alpha-helices in integral membrane proteins are recognized co-translationally and inserted into the membrane of the endoplasmic reticulum by the Sec61 translocon. A full quantitative description of this phenomenon, linking amino acid sequence to membrane insertion efficiency, is still lacking. Here, using in vitro translation of a model protein in the presence of dog pancreas rough microsomes to analyse a large number of systematically designed hydrophobic segments, we present a quantitative analysis of the position-dependent contribution of all 20 amino acids to membrane insertion efficiency, as well as of the effects of transmembrane segment length and flanking amino acids. The emerging picture of translocon-mediated transmembrane helix assembly is simple, with the critical sequence characteristics mirroring the physical properties of the lipid bilayer.Keywords
This publication has 29 references indexed in Scilit:
- Contribution of hydrophobic and electrostatic interactions to the membrane integration of the Shaker K + channel voltage sensor domainProceedings of the National Academy of Sciences of the United States of America, 2007
- Ez, a Depth-dependent Potential for Assessing the Energies of Insertion of Amino Acid Side-chains into Membranes: Derivation and Applications to Determining the Orientation of Transmembrane and Interfacial HelicesJournal of Molecular Biology, 2007
- Asn‐ and Asp‐mediated interactions between transmembrane helices during translocon‐mediated membrane protein assemblyEMBO Reports, 2006
- An amino acid “transmembrane tendency” scale that approaches the theoretical limit to accuracy for prediction of transmembrane helices: Relationship to biological hydrophobicityProtein Science, 2006
- A limited universe of membrane protein families and foldsProtein Science, 2006
- Effects of ‘hydrophobic mismatch’ on the location of transmembrane helices in the ER membraneFEBS Letters, 2001
- The Protein Data BankNucleic Acids Research, 2000
- Positively and negatively charged residues have different effects on the position in the membrane of a model transmembrane helixJournal of Molecular Biology, 1998
- Analysis of membrane and surface protein sequences with the hydrophobic moment plotJournal of Molecular Biology, 1984
- The nature of the accessible and buried surfaces in proteinsJournal of Molecular Biology, 1976