Document Detail


ClpP: A Structurally Dynamic Protease Regulated by AAA+ Proteins.
MedLine Citation:
PMID:  22595189     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Proteolysis is an important process for many aspects of the bacterial physiology. Clp proteases carry out a large proportion of protein degradation in bacteria. These enzymes assemble in complexes that combine the protease ClpP and the unfoldase, ClpA or ClpX. ClpP oligomerizes as two stacked heptameric rings enclosing a central chamber containing the proteolytic sites. ClpX and ClpA assemble into hexameric rings that bind both axial surfaces of the ClpP tetradecamer forming a barrel-like complex. ClpP requires association with ClpA or ClpX to unfold and thread protein substrates through the axial pore into the inner chamber where degradation occurs. A gating mechanism regulated by the ATPase exists at the entry of the ClpP axial pore and involves the N-terminal regions of the ClpP protomers. These gating motifs are located at the axial regions of the tetradecamer but in most crystal structures they are not visible. We also lack structural information about the ClpAP or ClpXP complexes. Therefore, the structural details of how the axial gate in ClpP is regulated by the ATPases are unknown. Here, we review our current understanding of the conformational changes that ClpA or ClpX induce in ClpP to open the axial gate and increase substrate accessibility into the degradation chamber. Most of this knowledge comes from the recent crystal structures of ClpP in complex with acyldepsipeptides (ADEP) antibiotics. These small molecules are providing new insights into the gating mechanism of this protease because they imitate the interaction of ClpA/ClpX with ClpP and activate its protease activity.
Authors:
John A Alexopoulos; Alba Guarné; Joaquin Ortega
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-14
Journal Detail:
Title:  Journal of structural biology     Volume:  -     ISSN:  1095-8657     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9011206     Medline TA:  J Struct Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Inc.
Affiliation:
Department of Biochemistry and Biomedical Sciences McMaster University, 1200 Main Street West, Hamilton, Ontario, L8N3Z5, Canada; MG. DeGroote Institute for Infectious Diseases Research, McMaster University, 1200 Main Street West, Hamilton, Ontario, L8N3Z5, Canada.
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