title: Recent Advances in Deciphering the Structure and Molecular Mechanism of the AAA+ ATPase N-Ethylmaleimide-Sensitive Factor (NSF).
abstract: N-ethylmaleimide-sensitive factor (NSF), first discovered in 1988, is a key factor for eukaryotic trafficking, including protein and hormone secretion and neurotransmitter release. It is a member of the AAA+ family (ATPases associated with diverse cellular activities). NSF disassembles soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes in conjunction with soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP). Structural studies of NSF and its complex with SNAREs and SNAPs (known as 20S supercomplex) started about 20years ago. Crystal structures of individual N and D2 domains of NSF and low-resolution electron microscopy structures of full-length NSF and 20S supercomplex have been reported over the years. Nevertheless, the molecular architecture of the 20S supercomplex and the molecular mechanism of NSF-mediated SNARE complex disassembly remained unclear until recently. Here we review recent atomic-resolution or near-atomic resolution structures of NSF and of the 20S supercomplex, as well as recent insights into the molecular mechanism and energy requirements of NSF. We also compare NSF with other known AAA+ family members.
authors.affiliation: Departments of Molecular and Cellular Physiology, Neurology and Neurological Sciences, Photon Science, and Structural Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
authors.forename: Minglei
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Departments of Molecular and Cellular Physiology, Neurology and Neurological Sciences, Photon Science, and Structural Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA. Electronic address: brunger@stanford.edu.
authors.forename: Axel T
authors.initials: AT
authors.lastname: Brunger
mesh_terms: D001692:Biological Transport; D018360:Crystallography, X-Ray; D056890:Eukaryota / Q000201:enzymology*; D008854:Microscopy, Electron; D008958:Models, Molecular; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D050600:SNARE Proteins / Q000378:metabolism
chemical_list: D050600:SNARE Proteins; D052066:N-Ethylmaleimide-Sensitive Proteins
keywords: ATPase; NSF; SNAREs; eukaryotic trafficking; protein disassembly