Document Detail


Mutations that alter RcdA surface residues decouple protein localization and CtrA proteolysis in Caulobacter crescentus.
MedLine Citation:
PMID:  19747489     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Periodic activation and deactivation of the essential transcriptional regulator CtrA is necessary to drive cell cycle progression in Caulobacter crescentus. At the onset of DNA replication (the G1-S cell cycle transition), CtrA and the AAA+ protease ClpXP colocalize at one cell pole along with three accessory proteins, RcdA, CpdR, and PopA, and CtrA is rapidly degraded. RcdA is required for polar sequestration and regulated proteolysis of CtrA in vivo, but it does not stimulate CtrA degradation by ClpXP in vitro; thus, the function of RcdA is unknown. We determined the 2.9-A-resolution crystal structure of RcdA and generated structure-guided mutations in rcdA. We assayed the ability of each RcdA variant to support CtrA proteolysis and polar protein localization in Caulobacter. Deletion of an intrinsically disordered peptide at the C-terminus of RcdA prevents efficient CtrA degradation and blocks the transient localization of RcdA and CtrA at the cell pole. Surprisingly, substitutions in two groups of highly conserved, charged surface residues disrupt polar RcdA or CtrA localization but do not affect CtrA proteolysis. This is the first report showing that localization of RcdA can be decoupled from its effects on CtrA degradation. In addition, we used epistasis experiments to show that RcdA is still required for regulated CtrA proteolysis when all SsrA-tagged proteins, abundant substrates of ClpXP, are absent from the cell. Our results argue that RcdA stimulates CtrA proteolysis neither by localizing CtrA at the cell pole nor by preventing competition from SsrA-tagged substrates.
Authors:
James A Taylor; Jeremy D Wilbur; Stephen C Smith; Kathleen R Ryan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-09-08
Journal Detail:
Title:  Journal of molecular biology     Volume:  394     ISSN:  1089-8638     ISO Abbreviation:  J. Mol. Biol.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-10-27     Completed Date:  2009-11-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985088R     Medline TA:  J Mol Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  46-60     Citation Subset:  IM    
Affiliation:
Department of Plant and Microbial Biology, 251 Koshland Hall, University of California, Berkeley, Berkeley, CA 94720-3102, USA.
Data Bank Information
Bank Name/Acc. No.:
PDB/3CTW
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / genetics*
Bacterial Proteins / chemistry*,  metabolism*
Caulobacter crescentus / cytology,  metabolism*
Cell Polarity
Crystallography, X-Ray
DNA-Binding Proteins / metabolism*
G1 Phase
Half-Life
Mutant Proteins / chemistry,  metabolism
Mutation / genetics*
Protein Binding
Protein Multimerization
Protein Processing, Post-Translational*
Protein Structure, Secondary
Protein Transport
S Phase
Sequence Deletion
Structure-Activity Relationship
Surface Properties
Transcription Factors / metabolism*
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Bacterial Proteins; 0/CtrA protein, Caulobacter; 0/DNA-Binding Proteins; 0/Mutant Proteins; 0/Transcription Factors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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