Membrane proteins: from sequence to structure

Abstract

The prediction of protein structure from sequence has been a long-standing goal of molecular biology. Integral membrane proteins, once abhorred by protein chemists and crystallographers because of their insolubility and stubborn refusal to yield good crystals, now appear to hold great promises for efficient structure prediction and engineering. This is mainly due to the constraints on permissible structures imposed by the lipid environment, and to the apparent uncoupling between an initial membrane targeting and insertion process which determines the overall topological arrangement of the transmembrane segments and a subsequent –condensation— of these segments into a unique folded state. Recent work suggests that the membrane insertion process is controlled by simple sequence elements composed of different combinations of long hydrophobic regions and flanking charged residues. In this review we sketch the most unportant structural rules relating amino acid sequence to membrane insertion to fully folded molecule, and their use for prediction and protein-engineering purposes.