Common Mode of Remodeling AAA ATPases p97/CDC48 by Their Disassembling Cofactors ASPL/PUX1
Copyright policy )Common Mode of Remodeling AAA ATPases p97/CDC48 by Their Disassembling Cofactors ASPL/PUX1
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.
- Charité - University Medicine Berlin Germany
- Freie Universität Berlin Germany
Adenosine Triphosphatases, Models, Molecular, Binding Sites, Arabidopsis Proteins, Amino Acid Motifs, Genetic Vectors, Arabidopsis, Coenzymes, Intracellular Signaling Peptides and Proteins, Gene Expression, Nuclear Proteins, Cell Cycle Proteins, Crystallography, X-Ray, Mutation, Escherichia coli, ATPases Associated with Diverse Cellular Activities, Humans, Cloning, Molecular, Carrier Proteins, Protein Binding
Adenosine Triphosphatases, Models, Molecular, Binding Sites, Arabidopsis Proteins, Amino Acid Motifs, Genetic Vectors, Arabidopsis, Coenzymes, Intracellular Signaling Peptides and Proteins, Gene Expression, Nuclear Proteins, Cell Cycle Proteins, Crystallography, X-Ray, Mutation, Escherichia coli, ATPases Associated with Diverse Cellular Activities, Humans, Cloning, Molecular, Carrier Proteins, Protein Binding
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).15 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!