Vacuolar protein sorting: two different functional states of the AAA-ATPase Vps4p.
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.
Hartmann
Claudia
C
Institute of Biochemistry, University of Zürich, Winterthurer Strasse 190, 8057 Zürich, Switzerland.
Chami
Mohamed
M
Zachariae
Ulrich
U
de Groot
Bert L
BL
Engel
Andreas
A
Grütter
Markus G
MG
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*
D056827:Endosomal Sorting Complexes Required for Transport; D029701:Saccharomyces cerevisiae Proteins; C107528:VPS4 protein, S cerevisiae; D000251:Adenosine Triphosphatases