Conformational Rearrangement of Fission DSPs

Dynamin superfamily proteins (DSPs) are large GTPases that play crucial roles in membrane remodeling processes, including vesicle uptake, mitochondrial fission, and opposing fusion events. Among them, dynamin and dynamin-related protein 1 (Drp1) share a conserved domain architecture, yet exhibit unique structural and regulatory features that tailor their functions. This review explores the conformational rearrangements of the mammalian fission DSPs, dynamin and Drp1, focusing on their dimeric and tetrameric structures, lipid-bound assemblies, and key regulatory elements that drive membrane constriction. Structural biology methods, including x-ray crystallography and cryo-electron microscopy, have provided insight into the mechanism of activation and constriction of these DSPs, revealing how domain interactions and intrinsically disordered regions regulate self-assembly and enzymatic activity. We briefly examine the role of sequence modifications and partner proteins in modulating DSP function, highlighting the impact of regulatory factors on their respective cellular functions. An ongoing goal is to better understand the molecular mechanisms governing the transitions from a pre-assembled cytosolic state to a self-assembled state for dynamin and Drp1 on membranes, which provides a foundation for studying subsequent helical constriction. This insight will enhance our knowledge of organelle dynamics and provide new avenues for therapeutic interventions targeting DSP-related pathologies.