Structural insight into the role of the Ton complex in energy transduction

• Published in: Nature (London) 2016-10, Vol.538 (7623), p.60-65
• Main Authors: Celia, Hervé, Noinaj, Nicholas, Zakharov, Stanislav D., Bordignon, Enrica, Botos, Istvan, Santamaria, Monica, Barnard, Travis J., Cramer, William A., Lloubes, Roland, Buchanan, Susan K.
• Format: Article
• Language: English
• Subjects: 14; 14/28; 631/326/41/2536; 631/535/1266; 631/57/1464; Bacteria; Biochemistry, Molecular Biology; Bioenergetics; Crystal structure; Crystallography; Crystallography, X-Ray; Cytoplasm; E coli; Energy metabolism; Escherichia coli - chemistry; Escherichia coli - ultrastructure; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - metabolism; Escherichia coli Proteins - ultrastructure; Gram-negative bacteria; Humanities and Social Sciences; Hydrogen-Ion Concentration; Life Sciences; Ligands; Membrane proteins; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Membrane Proteins - ultrastructure; Membranes; multidisciplinary; Multiprotein Complexes - chemistry; Multiprotein Complexes - metabolism; Multiprotein Complexes - ultrastructure; Observations; Physiological aspects; Proton-Motive Force; Science
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature19757

In Gram-negative bacteria, outer membrane transporters import nutrients by coupling to an inner membrane protein complex called the Ton complex. The Ton complex consists of TonB, ExbB, and ExbD, and uses the proton motive force at the inner membrane to transduce energy to the outer membrane via TonB. Here, we structurally characterize the Ton complex from Escherichia coli using X-ray crystallography, electron microscopy, double electron–electron resonance (DEER) spectroscopy, and crosslinking. Our results reveal a stoichiometry consisting of a pentamer of ExbB, a dimer of ExbD, and at least one TonB. Electrophysiology studies show that the Ton subcomplex forms pH-sensitive cation-selective channels and provide insight into the mechanism by which it may harness the proton motive force to produce energy. Structural studies shed light on the function and stoichiometry of the Ton complex, which harnesses the proton motive force across the bacterial inner membrane to transduce energy to the outer membrane. Ton complex structure and function The Ton complex is an inner membrane system in Gram-negative bacteria that, acting with outer membrane transporters, harnesses the proton motive force across the bacterial inner membrane to transduce energy to the outer membrane This tour-de-force study reports the first structural characterization of the Ton complex, composed of three transmembrane protein components, ExbB, ExbD and TonB. Using a combination of X-ray crystallography, electron microscopy and DEER spectroscopy, Susan Buchanan and colleagues provide unprecedented mechanistic insight into the function and stoichiometry of the Ton complex. Such insights are extensive to the homologous Tol and Mol complexes, which harness the proton motive force to generate mechanical energy.