系统发生学与进化生物学杂志

Evolutionary Interrelationships and Insights into Molecular Mechanisms of Functional Divergence: An Analysis of Neuronal Calcium Sensor Proteins

Abstract

Jeffrey Viviano, Hao Wu and Venkat Venkataraman

The normal function of any organism, its organizational complexity notwithstanding, depends on the interaction of its proteins with their targets. Thus, analysis of target site interaction is an essential part of all biology. At the protein level, such analyses are critical to both mechanistic knowledge and potential clinical applications such as drug discovery. Approaches to map amino acid residues involved in target site interaction typically are experimental or based on three-dimensional structures obtained through crystallography. Here we test a novel approach that combines phylogenetic analyses with mining of experimental data using neuronal calcium sensor proteins. The proteins fall into three groups based on sequence comparison. One interaction was taken up for analysis from each group. Using the sequence divergence to evaluate the role of amino acids identified experimentally to form the interface with the target, we demonstrate that it is possible to predict residues that are likely to contribute to the specificity of the interaction and, therefore, the functional divergence. Thus, evolutionary analyses of proteins provide an important addition in approaches to generate refined maps of target site interactions in proteins. This approach is especially useful in delineating the functional divergence in a family of closely related proteins.