title: Vacuolar protein sorting: two different functional states of the AAA-ATPase Vps4p.
abstract: The vacuolar protein sorting (Vps) pathway, in which Vps4 class I AAA-ATPases play a central role, regulates growth factor receptors, immune response, and developmental signaling, and participates in tumor suppression, apoptosis, and retrovirus budding. We present the first atomic structure of the nucleotide-free yeast His(6)DeltaNVps4p dimer and its AMPPNP (5'-adenylyl-beta,gamma-imidodiphosphate)-bound tetradecamer, derived from a cryo electron microscopy map. Vps4p dimers form two distinct heptameric rings and accommodate AAA cassettes in a head-to-head--not in a head-to-tail-fashion as in class II AAA-ATPases. Our model suggests a mechanism for disassembling ESCRT (endosomal sorting complex required for transport) complexes by movements of substrate-binding domains located at the periphery of the tetradecamer during ATP hydrolysis in one ring, followed by translocation through the central pore and ATP hydrolysis in the second ring.
authors.affiliation: Institute of Biochemistry, University of Zürich, Winterthurer Strasse 190, 8057 Zürich, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Hartmann
authors.forename: Mohamed
authors.initials: M
authors.lastname: Chami
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zachariae
authors.forename: Bert L
authors.initials: BL
authors.lastname: de Groot
authors.forename: Andreas
authors.initials: A
authors.lastname: Engel
authors.forename: Markus G
authors.initials: MG
authors.lastname: Grütter
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D003198:Computer Simulation; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D019281:Dimerization; D056827:Endosomal Sorting Complexes Required for Transport; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D014617:Vacuoles / Q000201:enzymology / Q000378:metabolism*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D029701:Saccharomyces cerevisiae Proteins; C107528:VPS4 protein, S cerevisiae; D000251:Adenosine Triphosphatases