ATP binding to neighbouring subunits and intersubunit allosteric coupling underlie proteasomal ATPase function

The primary functions of the proteasome are driven by a highly allosteric ATPase complex. ATP binding to only two subunits in this hexameric complex triggers substrate binding, ATPase–20S association and 20S gate opening. However, it is unclear how ATP binding and hydrolysis spatially and temporally...

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Main Authors:	Kim, Young-Chan, Snoberger, Aaron, Schupp, Jane, Smith, David M.
Format:	Online
Language:	English
Published:	Nature Pub. Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608255/

id	pubmed-4608255
recordtype	oai_dc
spelling	pubmed-46082552015-11-25 ATP binding to neighbouring subunits and intersubunit allosteric coupling underlie proteasomal ATPase function Kim, Young-Chan Snoberger, Aaron Schupp, Jane Smith, David M. Article The primary functions of the proteasome are driven by a highly allosteric ATPase complex. ATP binding to only two subunits in this hexameric complex triggers substrate binding, ATPase–20S association and 20S gate opening. However, it is unclear how ATP binding and hydrolysis spatially and temporally coordinates these allosteric effects to drive substrate translocation into the 20S. Here, we use FRET to show that the proteasomal ATPases from eukaryotes (RPTs) and archaea (PAN) bind ATP with high affinity at neighbouring subunits, which complements the well-established spiral-staircase topology of the 26S ATPases. We further show that two conserved arginine fingers in PAN located at the subunit interface work together as a single allosteric unit to mediate the allosteric effects of ATP binding, without altering the nucleotide-binding pattern. Rapid kinetics analysis also shows that ring resetting of a sequential hydrolysis mechanism can be explained by thermodynamic equilibrium binding of ATP. These data support a model whereby these two functionally distinct allosteric networks cooperate to translocate polypeptides into the 20S for degradation. Nature Pub. Group 2015-10-14 /pmc/articles/PMC4608255/ /pubmed/26465836 http://dx.doi.org/10.1038/ncomms9520 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Kim, Young-Chan Snoberger, Aaron Schupp, Jane Smith, David M.
spellingShingle	Kim, Young-Chan Snoberger, Aaron Schupp, Jane Smith, David M. ATP binding to neighbouring subunits and intersubunit allosteric coupling underlie proteasomal ATPase function
author_facet	Kim, Young-Chan Snoberger, Aaron Schupp, Jane Smith, David M.
author_sort	Kim, Young-Chan
title	ATP binding to neighbouring subunits and intersubunit allosteric coupling underlie proteasomal ATPase function
title_short	ATP binding to neighbouring subunits and intersubunit allosteric coupling underlie proteasomal ATPase function
title_full	ATP binding to neighbouring subunits and intersubunit allosteric coupling underlie proteasomal ATPase function
title_fullStr	ATP binding to neighbouring subunits and intersubunit allosteric coupling underlie proteasomal ATPase function
title_full_unstemmed	ATP binding to neighbouring subunits and intersubunit allosteric coupling underlie proteasomal ATPase function
title_sort	atp binding to neighbouring subunits and intersubunit allosteric coupling underlie proteasomal atpase function
description	The primary functions of the proteasome are driven by a highly allosteric ATPase complex. ATP binding to only two subunits in this hexameric complex triggers substrate binding, ATPase–20S association and 20S gate opening. However, it is unclear how ATP binding and hydrolysis spatially and temporally coordinates these allosteric effects to drive substrate translocation into the 20S. Here, we use FRET to show that the proteasomal ATPases from eukaryotes (RPTs) and archaea (PAN) bind ATP with high affinity at neighbouring subunits, which complements the well-established spiral-staircase topology of the 26S ATPases. We further show that two conserved arginine fingers in PAN located at the subunit interface work together as a single allosteric unit to mediate the allosteric effects of ATP binding, without altering the nucleotide-binding pattern. Rapid kinetics analysis also shows that ring resetting of a sequential hydrolysis mechanism can be explained by thermodynamic equilibrium binding of ATP. These data support a model whereby these two functionally distinct allosteric networks cooperate to translocate polypeptides into the 20S for degradation.
publisher	Nature Pub. Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608255/
_version_	1613489081581305856

ATP binding to neighbouring subunits and intersubunit allosteric coupling underlie proteasomal ATPase function

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