Abstract
Mitochondria are dynamic organelles that undergo cycles of fission and fusion. The yeast dynamin-related protein Dnm1 has been localized to sites of mitochondrial division. Using cryo-EM, we have determined the three-dimensional (3D) structure of Dnm1 in a GTP-bound state. The 3D map showed that Dnm1 adopted a unique helical assembly when compared with dynamin, which is involved in vesicle scission during endocytosis. Upon GTP hydrolysis, Dnm1 constricted liposomes and subsequently dissociated from the lipid bilayer. The magnitude of Dnm1 constriction was substantially larger than the decrease in diameter previously reported for dynamin. We postulate that the larger conformational change is mediated by a flexible Dnm1 structure that has limited interaction with the underlying bilayer. Our structural studies support the idea that Dnm1 has a mechanochemical role during mitochondrial division.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 20-27 |
| Number of pages | 8 |
| Journal | Nature Structural and Molecular Biology |
| Volume | 18 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2011 |
Funding
We thank D. Winkler and A. Steven for technical assistance in acquiring tomograms and P. Flicker, J. Hanover, W. Prinz, J. Evans and J. Heymann for critical discussions and reading of the manuscript. This work was supported by the Intramural Research Program of the US National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (J.E.H.) and the Nancy Nossal Fellowship of the NIH, NIDDK (J.A.M.). J.N. is supported by NIH grant R01GM062942, and L.L.L. is supported by NIH postdoctoral fellowship 1F32GM078749.
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology