合成ペプチドと膜の相互作用 膜タンパク質フォールディング原理の解明 モデル膜貫通ヘリックスによるアプローチ

Abstract

Hydrophobic lipid bilayer environment constrains transmembrane proteins mostly into an α-helical bundle structure. The folding processes of α-helical transmembrane proteins can be understood in terms of two energetically distinct stages, i.e. 1) independently stable transmembrane helices are formed and 2) the helices interact with each other to give a functional protein. The simplicity of the folding process enables us to use model transmembrane helices for elucidating driving forces working in membrane protein folding in the context of helix-helix interactions. Recent studies have devised several appropriate model peptides that form stable transmembrane helices and just started to quantitatively measure the helix-helix interactions in lipid bilayers. Possible driving forces involved in helix-helix and helix-lipid interactions are summarized. Statistical analyses of structure-known membrane proteins indicate diverse driving forces including the leucine zipper, the GlyXXXGly motif, network of hydrogen bonds and salt bridge.Furthermore, the lipid bilayer environment, which consists of diverse lipid species with asymmetric distributions in inner and outer leaflets, should have substantial effects on helix-helix interactions, therefore on the conformations of the whole proteins.