Structures of Asymmetric ClpX Hexamers Reveal Nucleotide-Dependent Motions in a AAA+ Protein-Unfolding Machine
Abstract
ClpX is a AAA+ machine that uses the energy of ATP binding and hydrolysis to unfold native proteins and translocate unfolded polypeptides into the ClpP peptidase. The crystal structures presented here reveal striking asymmetry in ring hexamers of nucleotide-free and nucleotide-bound ClpX. Asymmetry arises from large changes in rotation between the large and small AAA+ domains of individual subunits. These differences prevent nucleotide binding to two subunits, generate a staggered arrangement of ClpX subunits and pore loops around the hexameric ring, and provide a mechanism for coupling conformational changes caused by ATP binding or hydrolysis in one subunit to flexing motions of the entire ring. Our structures explain numerous solution studies of ClpX function, predict mechanisms for pore elasticity during translocation of irregular polypeptides, and suggest how repetitive conformational changes might be coupled to mechanical work during the ATPase cycle of ClpX and related molecular machines.
- Authors:
- Publication Date:
- Research Org.:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1006027
- Resource Type:
- Journal Article
- Journal Name:
- Cell
- Additional Journal Information:
- Journal Volume: 139; Journal Issue: (4) ; 11, 2009; Journal ID: ISSN 0092-8674
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 36 MATERIALS SCIENCE; ASYMMETRY; CONFORMATIONAL CHANGES; CRYSTAL STRUCTURE; ELASTICITY; HYDROLYSIS; NUCLEOTIDES; POLYPEPTIDES; PROTEINS; ROTATION; TRANSLOCATION
Citation Formats
Glynn, Steven E, Martin, Andreas, Nager, Andrew R, Baker, Tania A, Sauer, Robert T, and MIT,. Structures of Asymmetric ClpX Hexamers Reveal Nucleotide-Dependent Motions in a AAA+ Protein-Unfolding Machine. United States: N. p., 2010.
Web. doi:10.1016/j.cell.2009.09.034.
Glynn, Steven E, Martin, Andreas, Nager, Andrew R, Baker, Tania A, Sauer, Robert T, & MIT,. Structures of Asymmetric ClpX Hexamers Reveal Nucleotide-Dependent Motions in a AAA+ Protein-Unfolding Machine. United States. https://doi.org/10.1016/j.cell.2009.09.034
Glynn, Steven E, Martin, Andreas, Nager, Andrew R, Baker, Tania A, Sauer, Robert T, and MIT,. 2010.
"Structures of Asymmetric ClpX Hexamers Reveal Nucleotide-Dependent Motions in a AAA+ Protein-Unfolding Machine". United States. https://doi.org/10.1016/j.cell.2009.09.034.
@article{osti_1006027,
title = {Structures of Asymmetric ClpX Hexamers Reveal Nucleotide-Dependent Motions in a AAA+ Protein-Unfolding Machine},
author = {Glynn, Steven E and Martin, Andreas and Nager, Andrew R and Baker, Tania A and Sauer, Robert T and MIT,},
abstractNote = {ClpX is a AAA+ machine that uses the energy of ATP binding and hydrolysis to unfold native proteins and translocate unfolded polypeptides into the ClpP peptidase. The crystal structures presented here reveal striking asymmetry in ring hexamers of nucleotide-free and nucleotide-bound ClpX. Asymmetry arises from large changes in rotation between the large and small AAA+ domains of individual subunits. These differences prevent nucleotide binding to two subunits, generate a staggered arrangement of ClpX subunits and pore loops around the hexameric ring, and provide a mechanism for coupling conformational changes caused by ATP binding or hydrolysis in one subunit to flexing motions of the entire ring. Our structures explain numerous solution studies of ClpX function, predict mechanisms for pore elasticity during translocation of irregular polypeptides, and suggest how repetitive conformational changes might be coupled to mechanical work during the ATPase cycle of ClpX and related molecular machines.},
doi = {10.1016/j.cell.2009.09.034},
url = {https://www.osti.gov/biblio/1006027},
journal = {Cell},
issn = {0092-8674},
number = (4) ; 11, 2009,
volume = 139,
place = {United States},
year = {Tue Feb 02 00:00:00 EST 2010},
month = {Tue Feb 02 00:00:00 EST 2010}
}