A corkscrew model for dynamin constriction.
Numerous vesiculation processes throughout the eukaryotic cell are dependent on the protein dynamin, a large GTPase that constricts lipid bilayers. We have combined X-ray crystallography and cryo-electron microscopy (cryo-EM) data to generate a coherent model of dynamin-mediated membrane constriction. GTPase and pleckstrin homology domains of dynamin were fit to cryo-EM structures of human dynamin helices bound to lipid in nonconstricted and constricted states. Proteolysis and immunogold labeling experiments confirm the topology of dynamin domains predicted from the helical arrays. Based on the fitting, an observed twisting motion of the GTPase, middle, and GTPase effector domains coincides with conformational changes determined by cryo-EM. We propose a corkscrew model for dynamin constriction based on these motions and predict regions of sequence important for dynamin function as potential targets for future mutagenic and structural studies.
Mears
Jason A
JA
Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 8 Center Drive, MSC 0851, Bethesda, MD 20892, USA.
Ray
Pampa
P
Hinshaw
Jenny E
JE
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D034281:Dynamins / Q000737:chemistry* / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000378:metabolism; D007150:Immunohistochemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
D020558:GTP Phosphohydrolases; D034281:Dynamins