ESTIMATION OF STRUCTURAL SIMILARITY OF MEMBRANE-PROTEINS BY HYDROPATHY PROFILE ALIGNMENT

Many membrane proteins consist of bundles of a-helices that are reflec ted in typical hydropathy profiles of the amino acid sequences. The pr ofiles provide a link between the amino acid sequence of the polypepti de chain and its folding and are much better conserved during evolutio n than the amino acid sequences from which they are deduced. In this p aper, the hydropathy profiles are used to compare structures of membra ne proteins or families of membrane proteins. A technique is proposed that computes the optimal alignment of hydropathy profiles without mak ing use of the underlying sequences. The results show that two membran e proteins with only marginal sequence identity or two non-related fam ilies of membrane proteins can have very similar hydropathy profiles, indicating similar global structures. Two parameters are defined that measure differences between hydropathy profiles. The Structure Diverge nce Score (SDS) provides a measure for the divergence in profiles that reflect one and the same global structure. The SDS is derived from th e individual hydropathy profiles of the members of a homologous protei n family that are believed to share the same structure. The Profile Di fference Score (PDS) quantifies the difference between two hydropathy profiles. Comparison of the PDS of the optimal alignment of the hydrop athy profiles of two families of membrane proteins with the SDSs of th e two families provides a criterion for structural similarity. Using t his technique, pairwise alignment of the family profiles of eight fami lies of secondary transporters suggests that the families fall into fo ur structural classes.