Vacuolar Protein Sorting: Two Different Functional States of the AAA-ATPase Vps4p

C. Hartmann, M. Chami, Ulrich Zachariae, B.L. de Groot, A. Engel, M.G. Grütter

    Research output: Contribution to journalArticlepeer-review

    38 Citations (Scopus)

    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?NVps4p dimer and its AMPPNP (5'-adenylyl-ß,?-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.

    Original languageEnglish
    Pages (from-to)352-363
    Number of pages12
    JournalJournal of Molecular Biology
    Volume377
    Issue number2
    DOIs
    Publication statusPublished - 21 Mar 2008

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