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Nat Commun. 2015 Dec 11;6:10114. doi: 10.1038/ncomms10114.

Structure of a bacterial type III secretion system in contact with a host membrane in situ.

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Department of Crystallography, Institute of Structural and Molecular Biology, Birkbeck College, Malet Street, London WC1E 7HX, UK.
Focal Area Infection Biology, Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
Center for Cellular Imaging and NanoAnalytics, Biozentrum, University of Basel, Mattenstrasse 26, CH-4058 Basel, Switzerland.
Institute of Structural and Molecular Biology, Birkbeck and University College London, Malet Street, London WC1E 7HX, UK.


Many bacterial pathogens of animals and plants use a conserved type III secretion system (T3SS) to inject virulence effector proteins directly into eukaryotic cells to subvert host functions. Contact with host membranes is critical for T3SS activation, yet little is known about T3SS architecture in this state or the conformational changes that drive effector translocation. Here we use cryo-electron tomography and sub-tomogram averaging to derive the intact structure of the primordial Chlamydia trachomatis T3SS in the presence and absence of host membrane contact. Comparison of the averaged structures demonstrates a marked compaction of the basal body (4 nm) occurs when the needle tip contacts the host cell membrane. This compaction is coupled to a stabilization of the cytosolic sorting platform-ATPase. Our findings reveal the first structure of a bacterial T3SS from a major human pathogen engaged with a eukaryotic host, and reveal striking 'pump-action' conformational changes that underpin effector injection.

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