Biochemical implications of a three-dimensional model of monomeric actin bound to magnesium-chelated ATP

Actin structure is of intense interest in biology due to its importance in cell function and motility mediated by the spatial and temporal regulation of actin monomer-filament interconversions in a wide range of developmental and disease states. Despite this interest, the structure of many functionally important actin forms has eluded high-resolution analysis. Due to the propensity of actin monomers to assemble into filaments structural analysis of Mg-bound actin monomers has proven difficult, whereas high-resolution structures of actin with a diverse array of ligands that preclude polymerization have been quite successful. In this work, we provide a high-resolution structural model of the MgATP-actin monomer using a combination of computational methods and experimental foot-printing data that we have previously published. The key conclusion of this study is that the structure of the nucleotide binding cleft defined by subdomains 2 and 4 is essentially closed, with specific contacts between two subdomains predicted by the data.