INTEGRAL MEMBRANE-PROTEIN STRUCTURE - TRANSMEMBRANE ALPHA-HELICES AS AUTONOMOUS FOLDING DOMAINS

The transmembrane region of many integral membrane proteins is made up of a bundle of hydrophobic alpha-helices. Such a structure could result from a two-stage folding process, during which preformed transmembrane helices with independent stability pack without topological rearrangement. This view was originally prompted by experiments in which fragments of transmembrane regions were separately refolded into lipid bilayers and subsequently brought together to yield a functional protein. Other lines of evidence, including the existence of 'one-helix' miniproteins, gene-fusion experiments, helix-driven oligomerization of bitopic proteins, and sequence rearrangements in the course of evolution support this view. Although it forms a useful basis for structural predictions, the limitations of the two-stage folding hypothesis are not clearly defined, and the proportion of integral membrane proteins to which it applies remains uncertain. The papers discussed in the present review illustrate recent progress along these lines.