[Fundamental studies on membrane protein folding using model transmembrane helices].
To understand the folding process of alpha-helical membrane proteins in a lipid bilayer environment, the mechanisms of membrane partitioning and self-association of the helix should be elucidated. Considering the inhomogeneity of biological membranes composed of various lipids, not only the amino acid sequence of the transmembrane helices but also the composition of the lipid bilayers are determinants for folding and intramembrane distribution of membrane proteins thorough the balance between helix-helix, helix-lipid, and lipid-lipid interactions. Thermodynamic study using model transmembrane helices is fascinating to measure these complex interactions experimentally. The effects of lipid composition on membrane partitioning and self-association of an inert model transmembrane helix, (AALALAA)3, were examined. Partitioning of the helix into phosphoethanolamine-containing bilayers, gel-phase bilayers, or liquid ordered-phase bilayers significantly decreased, presumably by decreasing the fluidity in the hydrophobic region of the bilayer. It was found that the difference in the length of the hydrophobic regions between helix and lipid bilayers is energetically unfavorable, and partitioning into thicker and thinner membranes were weakened by increasing enthalpic and entropic terms, respectively. In contrast, stronger helix associations driven by the decrease in enthalpy were observed with increasing membrane thickness. These results demonstrate that the surrounding lipids are also important factors determining the behavior of transmembrane helices.
Yano
Yoshiaki
Y
Department of Analytical Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan. yyano@pharm.kyoto-u.ac.jp
D018257:Helix-Loop-Helix Motifs; D008565:Membrane Proteins / Q000737:chemistry; D008958:Models, Molecular; D017510:Protein Folding
D008565:Membrane Proteins