Document Detail


A scissor blade-like closing mechanism implicated in transmembrane signaling in a Bacteroides hybrid two-component system.
MedLine Citation:
PMID:  22532667     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Signaling across the membrane in response to extracellular stimuli is essential for survival of all cells. In bacteria, responses to environmental changes are predominantly mediated by two-component systems, which are typically composed of a membrane-spanning sensor histidine kinase and a cytoplasmic response regulator. In the human gut symbiont Bacteroides thetaiotaomicron, hybrid two-component systems are a key part of the bacterium's ability to sense and degrade complex carbohydrates in the gut. Here, we identify the activating ligand of the hybrid two-component system, BT4663, which controls heparin and heparan sulfate acquisition and degradation in this prominent gut microbe, and report the crystal structure of the extracellular sensor domain in both apo and ligand-bound forms. Current models for signal transduction across the membrane involve either a piston-like or rotational displacement of the transmembrane helices to modulate activity of the linked cytoplasmic kinases. The structures of the BT4663 sensor domain reveal a significant conformational change in the homodimer on ligand binding, which results in a scissor-like closing of the C-termini of each protomer. We propose this movement activates the attached intracellular kinase domains and represents an allosteric mechanism for bacterial transmembrane signaling distinct from previously described models, thus expanding our understanding of signal transduction across the membrane, a fundamental requirement in many important biological processes.
Authors:
Elisabeth C Lowe; Arnaud Baslé; Mirjam Czjzek; Susan J Firbank; David N Bolam
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-24
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-09     Completed Date:  2012-08-13     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7298-303     Citation Subset:  IM    
Affiliation:
Institute for Cell and Molecular Biosciences, Newcastle University, The Medical School, Newcastle upon Tyne NE2 4HH, United Kingdom.
Data Bank Information
Bank Name/Acc. No.:
PDB/4A2L;  4A2M
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MeSH Terms
Descriptor/Qualifier:
Bacterial Proteins / chemistry,  genetics,  metabolism*
Bacteroides / genetics,  metabolism*
Binding Sites / genetics
Cell Membrane / metabolism*
Crystallography, X-Ray
Heparin / metabolism
Heparitin Sulfate / metabolism
Humans
Intestines / metabolism,  microbiology
Models, Biological
Models, Molecular
Mutation
Periplasm / metabolism
Protein Binding
Protein Kinases / chemistry,  genetics,  metabolism
Protein Multimerization
Protein Structure, Tertiary
Signal Transduction*
Grant Support
ID/Acronym/Agency:
BB/F014163/1//Biotechnology and Biological Sciences Research Council
Chemical
Reg. No./Substance:
0/Bacterial Proteins; 9005-49-6/Heparin; 9050-30-0/Heparitin Sulfate; EC 2.7.-/Protein Kinases
Comments/Corrections

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