Structural Polymorphism in F-actin

Actin has maintained an exquisite degree of sequence conservation over large evolutionary distances for reasons that are not understood. Generating an atomic model of the actin filament (F-actin) has been driven by the desire to explain phenomena from muscle contraction to cytokinesis in mechanistic detail. Here we use electron cryo-microscopy to show that frozen-hydrated actin filaments contain a multiplicity of different structural states. We show (at ~ 10 Å resolution) that subdomain 2 can be disordered, as well as being able to make multiple contacts with the C-terminus of a subunit above it. We link a number of disease-causing mutations in the human ACTA1 gene to the most structurally dynamic elements of actin. Since F-actin is structurally polymorphic it cannot be described using only one atomic model, and must be understood as an ensemble of different states.