Allosteric communication induced by GTP binding sets off a closed-to-open transition in a bacterial dynamin-like protein

Dynamin superfamily proteins are mechanochemical GTPases that operate in highly oligomeric and highly cooperative superstructures to deform lipid membranes. It is known from the structures of a bacterial dynamin-like protein (BDLP) that binding of GTP and association of BDLP with lipids causes a transition from closed to open hinge 1 that affects oligomerization. We trace this radical, large-scale conformational change at the atomic level with unbiased, replica exchange, and umbrella sampling molecular dynamics simulations. We decipher how GTP loading from the GTPase domain to the distal stalk end is mediated by an allosteric network of salt bridges that act in response to GTP binding and subsequent conformational changes in GTPase domain motifs. Two previously undiscovered motifs have been identified whose movements free the paddle from the GTPase domain, allowing large-scale domain rearrangements. In addition, a novel wide-open state of BDLP reminiscent of human dynamin 1 is discovered. Our results explain several aspects of the BDLP cycle and have broad implications for other members of the dynamin family.