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Nucleotide-dependent conformational changes in dynamin: evidence for a mechanochemical molecular spring
M H Stowell1, B Marks, P Wigge
1MRC Laboratory of Molecular Biology, Cambridge, UK.
Nature Cell Biology
|November 13, 1999
Summary
Dynamin protein rings tighten during GTP hydrolysis, then expand, driving vesicle fission during endocytosis. This spring-like conformational change enhances dynamin
Area of Science:
- Molecular and Cell Biology
- Biochemistry
- Membrane Trafficking
Background:
- Dynamin (GTPase) is crucial for endocytosis, mediating vesicle fission.
- Clathrin-coated vesicles bud from the plasma membrane, requiring dynamin's function.
Purpose of the Study:
- Investigate dynamin's conformational changes during GTP hydrolysis.
- Elucidate the mechanism of dynamin-mediated vesicle fission.
Main Methods:
- Utilized phosphatidylinositol-4,5-bisphosphate lipid nanotubes as a membrane template.
- Employed electron microscopy to visualize dynamin ring structures.
- Assessed dynamin's GTPase activity and cooperativity.
Main Results:
- Dynamin rings tightly packed in GTP-bound state; spacing doubled after hydrolysis.
- Dynamin's GTPase activity on nanotubes was highly cooperative, increasing by 1000-fold.
- Increased Kcat, not Km, explained cooperativity in GTP hydrolysis.
Conclusions:
- A novel, lengthwise 'spring-like' conformational change in dynamin helix likely drives vesicle fission.
- Dynamin self-assembly on membrane templates reveals key mechanistic insights.
- GTP hydrolysis induces significant conformational and activity changes in dynamin.