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Common mode of remodeling AAA ATPases p97/CDC48 by their disassembling cofactors ASPL/PUX1

Authors

  • S. Banchenko
  • A. Arumughan
  • S. Petrović
  • D. Schwefel
  • E.E. Wanker
  • Y. Roske
  • U. Heinemann

Journal

  • Structure

Citation

  • Structure 27 (12): 1830-1841.e3

Abstract

  • The hexameric ring structure of the type II AAA+ ATPases is considered as stable and permanent. Recently, the UBX domain-containing cofactors Arabidopsis thaliana PUX1 and human alveolar soft part sarcoma locus (ASPL) were reported to bind and disassemble the cognate AAA+ ATPases AtCDC48 and human p97. Here, we present two crystal structures related to these complexes: a truncated AtCDC48 (AtCDC48-ND1) and a hybrid complex containing human p97-ND1 and the UBX domain of plant PUX1 (p97-ND1:PUX1-UBX). These structures reveal close similarity between the human and plant AAA+ ATPases, but also highlight differences between disassembling and non-disassembling AAA+ ATPase cofactors. Based on an AtCDC48 disassembly assay with PUX1 and known crystal structures of the p97-bound human cofactor ASPL, we propose a general ATPase disassembly model. Thus, our structural and biophysical investigations provide detailed insight into the mechanism of AAA+ ATPase disassembly by UBX domain cofactors and suggest a general mode of regulating the cellular activity of these molecular machines.


DOI

doi:10.1016/j.str.2019.10.001