# Conformational Rearrangement of Fission DSPs

## TL;DR

This paper reviews how dynamin and Drp1 proteins change shape to help cells reshape membranes, focusing on their structural changes and regulation.

## Contribution

The paper provides a detailed analysis of the conformational dynamics and regulatory mechanisms of fission DSPs, emphasizing their structural transitions.

## Key findings

- Fission DSPs transition from cytosolic states to membrane-bound assemblies through partner proteins or lipid interactions.
- Structural biology reveals how domain interactions and disordered regions regulate DSP self-assembly and activity.
- Understanding these mechanisms could lead to new therapeutic strategies for DSP-related diseases.

## Abstract

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.

Assembly properties of fission DSPs. Fission DSPs exist in a dynamic equilibrium of oligomer states in the cytosol, where they must be activated by partner proteins or lipid to induce assembly, and upon GTP hydrolysis, constriction.