A Pseudoatomic Model of the Dynamin Polymer Identifies a Hydrolysis-Dependent Powerstroke

TLDR

The GTPase dynamin catalyzes membrane fission by forming a collar around clathrin‑coated pit necks, yet the specific structural interactions and conformational changes that drive this process remain unclear. The study presents GMPPCP‑bound structures of a truncated human dynamin 1 helical polymer and a GG fusion protein to investigate dynamin’s architecture. The authors determined structures at 12.2 Å and 2.2 Å and used chemical crosslinking to show that dynamin tetramers consist of two dimers with trans G‑domain–GED interactions. The structures reveal that G‑domain dimers form only between tetramers in sequential rungs and that a hydrolysis‑dependent powerstroke may drive membrane remodeling during fission.

Abstract

The GTPase dynamin catalyzes membrane fission by forming a collar around the necks of clathrin-coated pits, but the specific structural interactions and conformational changes that drive this process remain a mystery. We present the GMPPCP-bound structures of the truncated human dynamin 1 helical polymer at 12.2 Å and a fusion protein, GG, linking human dynamin 1's catalytic G domain to its GTPase effector domain (GED) at 2.2 Å. The structures reveal the position and connectivity of dynamin fragments in the assembled structure, showing that G domain dimers only form between tetramers in sequential rungs of the dynamin helix. Using chemical crosslinking, we demonstrate that dynamin tetramers are made of two dimers, in which the G domain of one molecule interacts in trans with the GED of another. Structural comparison of GGGMPPCP to the GG transition-state complex identifies a hydrolysis-dependent powerstroke that may play a role in membrane-remodeling events necessary for fission.