PEDS Advance Access originally published online on September 23, 2004
Protein Engineering Design and Selection 2004 17(8):613-624; doi:10.1093/protein/gzh072
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Computational analysis of 
-helical membrane protein structure: implications for the prediction of 3D structural models
1Department of Biology, University College London, Darwin Building, Gower Street, London WC1E 6BT and 2European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK
3 To whom correspondence should be addressed. E-mail: thornton{at}ebi.ac.uk
Relatively little has been known about the structure of 
-helical membrane proteins, since until recently few structures had been crystallized. These limited data have restricted structural analyses to the prediction of secondary structure, rather than tertiary folds. In order to address this, this paper describes an analysis of the 23 available membrane protein structures. A number of findings are made that are of particular relevance to transmembrane helix packing: (1) on average lipid-tail-accessible transmembrane residues are significantly more hydrophobic, less conserved and contain different residue types to buried residues; (2) charged residues are not always buried and, when accessible to membrane lipid tails, few are paired with another charge and instead they often interact with phospholipid head-groups or with other residue types; (3) a significant proportion of lipid-tail-accessible charged and polar residues form hydrogen bonds only with residues one turn away in the same helix (intra-helix); (4) pore-lining residues are usually hydrophobic and it is difficult to distinguish them from buried residues in terms of either residue type or conservation; and (5) information was gained about the proportion of helices that tend to contribute to lining a pore and the resulting pore diameter. These findings are discussed with relevance to the prediction of membrane protein 3D structure.
Received April 23, 2004; revised August 25, 2004; accepted August 26, 2004.
Edited by Andrej Sali
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