Membrane Constriction by Dynamin through GTP-Driven Conformational Changes from Coarse-Grained Molecular Dynamics Simulations
Dynamin, a GTPase involved in membrane remodeling processes, plays a pivotal role in membrane fission during endocytosis. Understanding the molecular mechanisms of dynamin assembly and its conformational change triggered by GTP hydrolysis on lipid membranes is crucial for elucidating the intricate details of membrane constriction and fission events. However, the size and complexity of the dynamin assembly prevent us from obtaining comprehensive molecular mechanisms. In this study, we performed coarse-grained molecular dynamics (CG-MD) simulations to elucidate the chemo-mechanical coupling mechanism of dynamin membrane constriction. We set up a CG Martini simulation system that contains dynamin rings on a tubular membrane with realistic molecular structures. Controlling the length of the tubular membrane with a pressure coupling, we simulate membrane constriction through the nucleotide-state-dependent conformational change of dynamin. The simulation results suggest that the conformational change to the GDP state loosens and expands the dynamin rings, resulting in indirect membrane constriction in the protein-uncoated region. This study lays the groundwork for simulating the chemo-mechanical coupling of dynamin-mediated membrane constriction.
Authors
- Md. Iqbal Mahmood (ORCID: https://orcid.org/0000-0002-5762-9075)
- Kei-ichi Okazaki (ORCID: https://orcid.org/0000-0003-2168-3069)
- Hiroshi Noguchi (ORCID: https://orcid.org/0000-0003-1735-7586)
- Shintaroh Kubo (ORCID: https://orcid.org/0000-0002-0946-8879)
Institutions
- National Institutes of Natural Sciences (JP)
- The Graduate University for Advanced Studies, SOKENDAI (JP)
- Hoshi University (JP)
- Institute for Solid State Physics and Optics (HU)
- EarthTech International (United States) (US)
- Nippon Soken (Japan) (JP)
- Institute for Molecular Science (JP)
- Pharmaceutical Biotechnology (Czechia) (CZ)
- The University of Tokyo (JP)
Publication Details
- Journal
- The Journal of Physical Chemistry Letters
- Published
- 2025-11-21
- DOI
- https://doi.org/10.1021/acs.jpclett.5c02867
- Primary Topic
- Lipid Membrane Structure and Behavior
- Type
- article
- Field-Weighted Citation Impact
- 0.00