Supramolecular SNARE assembly precedes hemifusion in SNARE-mediated membrane fusion.
Formation of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex facilitates intracellular membrane fusion. A single SNARE complex is thought to be insufficient; multiple copies of SNARE complexes must work cooperatively. However, the mechanism by which such a higher-order SNARE protein structure is assembled is unknown. EPR and fluorescence analyses show that at least three copies of target-membrane SNARE proteins self-assemble through the interaction between the transmembrane domains (TMDs), and this multimeric structure serves as scaffolding for trans-SNARE assembly. SNARE core formation in solution induces oligomerization of the TMDs of vesicle-associated SNAREs in the apposing membrane, transiently forming a supramolecular protein structure spanning two membranes. This higher-order protein intermediate evolves, by involving lipid molecules, to the hemifusion state. Hemifusion is subsequently followed by distal leaflet mixing and formation of the cis-SNARE complex.
Lu
Xiaobing
X
Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, Iowa 50011, USA.
Zhang
Yinghui
Y
Shin
Yeon-Kyun
YK
D004578:Electron Spin Resonance Spectroscopy; D005453:Fluorescence; D007700:Kinetics; D008561:Membrane Fusion / Q000502:physiology*; D008954:Models, Biological; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D050765:Qa-SNARE Proteins / Q000737:chemistry / Q000378:metabolism; D050600:SNARE Proteins / Q000737:chemistry* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism
D050765:Qa-SNARE Proteins; D050600:SNARE Proteins; C084006:SSO1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins