Nucleotide-dependent control of internal strains in ring-shaped AAA+ motors.

The AAA+ (ATPase Associated with various cellular Activities) machinery represents an extremely successful and widely used design plan for biological motors. Recently found crystal structures are beginning to reveal nucleotide-dependent conformational changes in the canonical hexameric rings of the AAA+ motors. However, the physical mechanism by which ATP binding on one subunit allosterically propagates across the entire ring remains to be found. Here we analyze and compare structural organization of three ring-shaped AAA+ motors, ClpX, HslU, and dynein. By constructing multimers using subunits of identical conformations, we find that individual subunits locally possess helical geometries with varying pitch, radius, chirality, and symmetry number. These results suggest that binding of an ATP to a subunit imposes conformational constraint that must be accommodated by more flexible nucleotide-free subunits to relieve mechanical strain on the ring. Local deformation of the ring contour and subsequent propagation of strains may be a general strategy that AAA+ motors adopt to generate force while achieving functional diversity.