Lipid recognition propensities of amino acids in membrane proteins from atomic resolution data
1 Department of Fundamental Research, National Institute of Biomedical Innovation, 7-6-8 Saito Asagi, Ibaraki, Osaka, Japan
2 Institute of Bioinformatics Research and Development, Japan Science and Technology Agency, 5-3 Yonbancho, Chiyoda-ku, Tokyo, Japan
3 RIKEN Quantitative Biology Center, 7-1-26 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, Japan
4 RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako-shi, Saitama, Japan
5 RIKEN Advanced Institute for Computational Science, 7-1-26 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, Japan
Citation and License
BMC Biophysics 2011, 4:21 doi:10.1186/2046-1682-4-21Published: 14 December 2011
Protein-lipid interactions play essential roles in the conformational stability and biological functions of membrane proteins. However, few of the previous computational studies have taken into account the atomic details of protein-lipid interactions explicitly.
To gain an insight into the molecular mechanisms of the recognition of lipid molecules by membrane proteins, we investigated amino acid propensities in membrane proteins for interacting with the head and tail groups of lipid molecules. We observed a common pattern of lipid tail-amino acid interactions in two different data sources, crystal structures and molecular dynamics simulations. These interactions are largely explained by general lipophilicity, whereas the preferences for lipid head groups vary among individual proteins. We also found that membrane and water-soluble proteins utilize essentially an identical set of amino acids for interacting with lipid head and tail groups.
We showed that the lipophilicity of amino acid residues determines the amino acid preferences for lipid tail groups in both membrane and water-soluble proteins, suggesting that tightly-bound lipid molecules and lipids in the annular shell interact with membrane proteins in a similar manner. In contrast, interactions between lipid head groups and amino acids showed a more variable pattern, apparently constrained by each protein's specific molecular function.