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

TY - JOUR

T1 - Vacuolar Protein Sorting

T2 - Two Different Functional States of the AAA-ATPase Vps4p

AU - Hartmann, C.

AU - Chami, M.

AU - Zachariae, Ulrich

AU - de Groot, B.L.

AU - Engel, A.

AU - Grütter, M.G.

N1 - MEDLINE® is the source for the MeSH terms of this document.

PY - 2008/3/21

Y1 - 2008/3/21

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/40049105414

U2 - 10.1016/j.jmb.2008.01.010

DO - 10.1016/j.jmb.2008.01.010

M3 - Article

AN - SCOPUS:40049105414

SN - 0022-2836

VL - 377

SP - 352

EP - 363

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

IS - 2

ER -