Conservation of substructures in proteins:: Interfaces of secondary structural elements in proteasomal subunits

It is observed that during divergent evolution of two proteins with a common phylogenetic origin, the structural similarity of their backbones is often preserved even when the sequence similarity between them decreases to a virtually undetectable level. Here we analyzed,whether the conservation of structure along evolution involves also the local atomic structures in the interfaces between secondary structural elements. We have used as study case one protein family, the proteasomal subunits, for which 17 crystal structures are known. These include 14 different subunits of Saccharomyces cerevisiae, 2 subunits of Thermoplasma acidophilum and one subunit of Escherichia coli. The structural core of the 17 proteasomal subunits has 23 secondary structural elements. Any two adjacent secondary structural elements form a molecular interface consisting of two molecular patches. We found 61 interfaces that occurred in all 17 subunits. The 3D shape of equivalent molecular patches from different proteasomal subunits were compared by superposition. Our results demonstrate that pairs of equivalent molecular patches show an RMSD which is lower than that of randomly chosen patches from unrelated proteins. This is true even when patch comparisons with identical residues were excluded from the analysis. Furthermore it is known that the sequential dissimilarity is correlated to the RMSD between the backbones of the members of protein families. The question arises whether this is also true for local atomic structures. The results show that the correlation of individual patch RMSD values and local sequence dissimilarities is low and has a wide range from 0 to 0.41, however, it is surprising that there is a good correlation between the average RMSD of all corresponding patches and the global sequence dissimilarity. This average patch RMSD correlates slightly stronger than the C-alpha-trace RMSD to the global sequence dissimilarity. (C) 2000 Academic Press.