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PMID: 18508076 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Kinetic partitioning between alternative protein-protein interactions controls a transcriptional switch.

Journal of molecular biology ·Vol. 380 ·No. 1 ·2008-06-27 ·Pages 223-36

Zhao H, Beckett D

Abstract

Proteins can perform completely distinct functions in response to the particular partners that they bind to. Consequently, determination of the mechanism of functional regulation in such systems requires elucidation of the mechanism switching between binding partners. The central protein of the Escherichia coli biotin regulatory system, BirA, switches between its function as a metabolic enzyme or a transcriptional repressor in response to binding either the biotin carboxyl carrier protein subunit of acetyl-CoA carboxylase or a second BirA monomer. These two protein-protein interactions are structurally mutually exclusive. The results of earlier studies suggest that the system is regulated by kinetic partitioning between the two protein-protein interactions. In this work, sedimentation velocity was employed to monitor the partitioning directly. The results indicate similar equilibrium parameters governing formation of the two protein-protein interactions. Kinetic analysis of the sedimentation velocity data indicated that holoBirA dimerization is governed by very slow forward and reverse rate constants. The slow kinetics of holoBirA dimerization combined with fluctuations in the intracellular apoBCCP pool are critical determinants in partitioning BirA between its distinct biological functions.

MeSH Terms
Adenosine Triphosphate/metabolism Biotin/metabolism Carbon-Nitrogen Ligases/genetics,metabolism Catalysis Centrifugation DNA Footprinting Deoxyribonucleases/metabolism Dimerization Escherichia coli/genetics,metabolism Escherichia coli Proteins/genetics,metabolism Kinetics Protein Binding Repressor Proteins/genetics,metabolism Temperature Transcription Factors/genetics,metabolism Transcription, Genetic
Chemicals
Escherichia coli Proteins Repressor Proteins Transcription Factors Biotin Adenosine Triphosphate Deoxyribonucleases Carbon-Nitrogen Ligases birA protein, E coli
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Zhao Huaying
Department of Chemistry and Biochemistry, Center for Biological Structure and Organization, University of Maryland, College Park, MD 20742, USA.
Beckett Dorothy
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Article Info
Journal
Journal of molecular biology
Abbr.
J Mol Biol
ISSN
1089-8638
DOI
10.1016/j.jmb.2008.04.068
Published
2008-06-27
Epub
2008-00-03
Pages
223-36
Language
English
Region
England
NLM ID
2985088R
PMCID
PMC2566847
Subset
IM
Grants
NCRR NIH HHS · S10 RR015899-01A1 · United States
NIGMS NIH HHS · R01 GM046511-18 · United States
NIGMS NIH HHS · R01 GM046511 · United States
NCRR NIH HHS · S10-RR15899 · United States
NIGMS NIH HHS · R01 GM46511 · United States
External Links
PubMed source DOI: 10.1016/j.jmb.2008.04.068 PMC Full Text View journal details
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