Determining the roles of different chain fragments in recognition of immunoglobulin fold

We examine sequence-to-structure specificity of β-structural fragments of immunoglobulin domains. The structure specificity of separate chain fragments is estimated by computing the Z-score values in recognition of the native structure in gapless threading tests. To improve the accuracy of our calculations we use energy averaging over diverse homologs of immunoglobulin domains. We show that the interactions between residues of β-structure are more determinant in recognition of the native structure than the interactions within the whole chain molecule. This result distinguishes immunoglobulins from more typical proteins where the interactions between residues of the whole chain normally recognize the native fold more accurately than interactions between the residues of the secondary structure residues alone [Reva,B. and Topiol,S. (2000) Biocomputing: Proceedings of the Pacific Symposium. World Scientific Publishing Co., pp. 168-178]. We also find that the predominant contributions of the secondary structure are produced by the four central β-strands that form the core of the molecule. The results of this study allow us through quantitative means to understand the architecture of immunoglobulin molecules. Comparing the fold recognition data for different chain fragments one can say that β-strands form a rigid frame for immunoglobulin molecules, whereas loops, with no structural role, can develop a broad variety of binding specificities. It is well known that protein function is determined by specific portions of a protein chain. This study suggests that the whole protein structure can be predominantly determined by a few fragments of chain which form the structural framework of the molecule. This idea may help in better understanding the mechanisms of protein evolution: strengthening a protein structure in the key framework-forming regions allows mutations and flexibility in other chain regions.