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A scissor blade-like closing mechanism implicated in transmembrane signaling in a Bacteroides hybrid two-component system

DOI: 10.1073/pnas.1200479109 DOI Help
PMID: 22532667 PMID Help

Authors: E. C. Lowe (Newcastle University) , A. Basle (Newcastle University) , M. Czjzek (Université Pierre et Marie Curie, Université Paris 6, Centre National de la Recherche Scientifique, Roscoff, France) , S. J. Firbank (Newcastle University) , D. N. Bolam (Newcastle University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Proceedings Of The National Academy Of Sciences , VOL 109 (19) , PAGES 7298 - 7303

State: Published (Approved)
Published: May 2012
Diamond Proposal Number(s): 1221

Abstract: 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.

Journal Keywords: Bacteroides; Binding; Cell; Crystallography; X-Ray; Heparin; Heparitin; Humans; Intestines; Models; Biological; Models; Molecular; Mutation; Periplasm; Protein; Tertiary; Signal Transduction

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography , I04-Macromolecular Crystallography

Added On: 26/09/2012 14:37

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