Analysis of 3D structural differences in the IgG-binding domains based on the interresidue average-distance statistics.

It is well-known that the IgG-binding domain from staphylococcal protein A folds into a 3 alpha helix bundle structure, while the IgG-binding domain of streptococcal protein G forms an (alpha + beta) structure. Recently, He et al. (Biochemistry 44:14055-14061, 2005) made mutants of these proteins from the wild types of protein A and protein G strains. These mutants are referred to as protein A219 and protein G311, and it was showed that these two mutants have different 3D structures, i.e., the 3 alpha helix bundle structure and the (alpha + beta) structure, respectively, despite the high sequence identity (59%). The purpose of our study was to clarify how such 3D structural differences are coded in the sequences with high homology. To address this problem, we introduce a predicted contact map constructed based on the interresidue average-distance statistics for prediction of folding properties of a protein. We refer to this map as an average distance map (ADM). Furthermore, the statistics of interresidue distances can be converted to an effective interresidue potential. We calculated the contact frequency of each residue of a protein in random conformations with this effective interresidue potential, and then we obtained values similar to phi values. We refer to this contact frequency of each residue as a p(mu) value. The comparison of the p(mu) values to the phi values for a protein suggests that p(mu) values reveal the information on the folding initiation site. Using these techniques, we try to extract the information on the difference in the 3D structures of protein A219 and protein G311 coded in their amino acid sequences in the present work. The results show that the ADM analyses and the p(mu) value analyses predict the information of folding initiation sites, which can be used to detect the 3D difference in both proteins.