Structure-based Approaches to Protein Recognition

Julian Mintseris, Boston University

Recent analyses of high-throughput protein interaction data coupled with large-scale investigations of evolutionary properties of interaction networks have left some unanswered questions. To what extent do protein interactions act as constraints during evolution of the protein sequence? How does the type of interaction, specifically transient or obligate, play into these constraints? Are the mutations in the binding site of an interacting protein correlated with mutations in the binding site of its partner? We undertake to answer these questions relying on a carefully compiled dataset of protein complex structures. Results point to the importance of distinguishing between transient and obligate interactions. We conclude that residues in the interfaces of obligate complexes tend to evolve at a relatively slower rate, allowing them to co-evolve with their interacting partners. In contrast, the plasticity inherent in transient interactions leads to increased rate of substitution for the interface residues and leaves little or no evidence of correlated mutation.

Abstract Author(s): Julian Mintseris & Zhiping Weng