Lipophobicity and the residue environments of the transmembrane α-helical bundle

Younes Mokrab, Tim J. Stevens, Kenji Mizuguchi

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

We present a statistical analysis of residue environment preferences along the membrane normal in helical transmembrane (HTM) proteins, based on an up-to-date nonredundant set of protein structures. Distinct amino acid residue propensities were revealed, both in terms of lipid accessibility and depth within the lipid bilayer, highlighting their potential usefulness for alignment and modelling of membrane proteins. Using the propensities in the HTM proteins, new lipophobicity scales (LIPS) were derived for the lipid bilayer interface (LI) and the hydrocarbon core (HC) regions of the membrane, measuring the tendencies of different amino acids to occupy protein-buried or lipid-exposed positions. The LIPS for LI and HC resemble some of the existing LIPS such as kPROT, TMLIP2, and LA but our new scales were derived by using more comprehensive information than any of the existing scales and are distinct overall. Effective free energies of transfer derived from the LIPS showed a good correlation with a semi empirical scale for the transfer energies from the interface of palmitoyloleoylphosphocholine (POPC) bilayers to ocatanol (AWW ioct). The new scales also predicted the lipophobic effect in the LI to be smaller than the hydrophobic effect governing the folding of globular proteins, consistent with theory and experiment. These results provided a coherent description of lipophobicitliy in the distinct layers of the membrane and gave clarity to the widely discussed notion of whether membrane proteins can be regarded as ''inside out'' of globular proteins.

Original languageEnglish
Pages (from-to)32-49
Number of pages18
JournalProteins: Structure, Function and Bioinformatics
Volume74
Issue number1
DOIs
Publication statusPublished - Jan 2009
Externally publishedYes

Fingerprint

Lipid Bilayers
Lipid bilayers
Energy Transfer
Hydrocarbons
Proteins
Membranes
Membrane Proteins
Lipids
Amino Acids
Protein Folding
Energy transfer
Free energy
Statistical methods
Experiments

Keywords

  • Amino acid propensity
  • Helical transmembrane proteins
  • Lipid bilayer
  • Local structure environment
  • Protein structure
  • Structural bioinformatics

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Molecular Biology

Cite this

Lipophobicity and the residue environments of the transmembrane α-helical bundle. / Mokrab, Younes; Stevens, Tim J.; Mizuguchi, Kenji.

In: Proteins: Structure, Function and Bioinformatics, Vol. 74, No. 1, 01.2009, p. 32-49.

Research output: Contribution to journalArticle

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