Mechanisms of Protein-Protein Sliding: Coiled Coils as a Tool Model

Abstract

The alpha-helical coiled coil domain is a ubiquitous protein motif found in approximately 5% of all translated protein sequences. Due to the relative simplicity of the sequence/structure relationship, coiled coils have been extensively studied, leading the emergence of novel protein design and engineering techniques. Nevertheless, a complete understanding of coiled coils structure and their dynamics is still far from being achieved. For instance, it has been experimentally observed that coiled coils exhibit staggered conformations that are generated after sliding events between two helixes. Using structure-based modeling techniques as well as coiled coil design tools, we study the mechanisms of sliding for parallel and antiparallel homodimer coiled coil conformations. We are motivated at characterizing the molecular determinants that govern the kinetics and dynamics of sliding in coiled coils and to predict its prevalence in natural coiled-coil proteins.