A sequence and structural study of transmembrane helices

A comparison is made between the distribution of residue preferences, three dimensional nearest neighbour contacts, preferred rotamers, helix-helix cr ossover angles and peptide bond angles in three sets of proteins: a non-red undant set of accurately determined globular protein structures, a set of f our-helix bundle structures and a set of membrane protein structures. Resid ue preferences for the latter two sets may reflect overall helix stabilisin g propensities but may also highlight differences arising out of the contra sting nature of the solvent environments in these two cases. The results be ar out the expectation that there may be differences between residue type p references in membrane proteins and in water soluble globular proteins. For example, the beta -branched residue types valine and isoleucine are consid erably more frequently encountered in membrane helices. Likewise, glycine a nd proline, residue types normally associated with 'helix-breaking' propens ity are found to be relatively more common in membrane helices. Three dimen sional nearest neighbour contacts along the helix, preferred rotamers, and peptide bond angles are very similar in the three sets of proteins as far a s can be ascertained within the limits of the relatively low resolution of the membrane proteins dataset. Crossing angles for helices in the membrane protein set resemble the four helix bundle set more than the general non-re dundant set, but in contrast to both sets they have smaller crossing angles consistent with the dual requirements for the helices to form a compact st ructure while having to span the membrane. In addition to the pairwise pack ing of helices we investigate their global packing and consider the questio n of helix supercoiling in helix bundle proteins.