title: Geometric catalysis of membrane fission driven by flexible dynamin rings.
abstract: Biological membrane fission requires protein-driven stress. The guanosine triphosphatase (GTPase) dynamin builds up membrane stress by polymerizing into a helical collar that constricts the neck of budding vesicles. How this curvature stress mediates nonleaky membrane remodeling is actively debated. Using lipid nanotubes as substrates to directly measure geometric intermediates of the fission pathway, we found that GTP hydrolysis limits dynamin polymerization into short, metastable collars that are optimal for fission. Collars as short as two rungs translated radial constriction to reversible hemifission via membrane wedging of the pleckstrin homology domains (PHDs) of dynamin. Modeling revealed that tilting of the PHDs to conform with membrane deformations creates the low-energy pathway for hemifission. This local coordination of dynamin and lipids suggests how membranes can be remodeled in cells.
authors.affiliation: Biophysics Unit (CSIC, UPV/EHU) and Department of Biochemistry and Molecular Biology, University of the Basque Country, Leioa, Spain.
authors.forename: Anna V
authors.initials: AV
authors.lastname: Shnyrova
authors.forename: Pavel V
authors.initials: PV
authors.lastname: Bashkirov
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Akimov
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Pucadyil
authors.forename: Joshua
authors.initials: J
authors.lastname: Zimmerberg
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Schmid
authors.forename: Vadim A
authors.initials: VA
authors.lastname: Frolov
mesh_terms: D055162:Biocatalysis; D034284:Dynamin I / Q000737:chemistry* / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006868:Hydrolysis; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D043942:Nanotubes; D011487:Protein Conformation; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D006160:Guanosine Triphosphate; D034284:Dynamin I