One of the central paradigms of structural biology is that membrane proteins are 'inside-out' proteins, in that they have a core of polar residues surrounded by apolar residues. This is the reverse of the characteristics found in water-soluble proteins. We have decided to test this paradigm, now that sufficient numbers of transmembrane α-helical structures are accessible to statistical analysis. We have analyzed the correlation between accessibility and hydrophobicity of both individual residues and complete helices. Our analyses reveal that hydrophobicity of residues in a transmembrane helical bundle does not correlate with any preferred location and that the hydrophilic vector of a helix is a poor indicator of the solvent exposed face of a helix. Neither polar nor hydrophobic residues show any bias for the exterior or the interior of a transmembrane domain. As a control, analysis of water-soluble helical bundles performed in a similar manner has yielded clear correlations between hydrophobicity and accessibility. We therefore conclude that, based on the data set used, membrane proteins as 'indicate-out' proteins is an unfounded notion, suggesting that packing of α-helices in membranes is better understood by maximization of van der Waal's forces, rather than by a general segregation of hydrophobicities driven by lipid exclusion.
|Number of pages
|Proteins: Structure, Function and Genetics
|Published - 1 Jul 1999
- Protein folding
- Protein structure