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They are activated by contact with eukaryotic cells and inject virulence proteins inside them. Host cell detection requires a protein complex located at the tip of the device's external injection needle. The\n                    <jats:italic>Shigella<\/jats:italic>\n                    tip complex (\n                    <jats:styled-content style=\"fixed-case\">TC<\/jats:styled-content>\n                    ) is composed of\n                    <jats:styled-content style=\"fixed-case\">IpaD<\/jats:styled-content>\n                    , a hydrophilic protein, and IpaB, a hydrophobic protein, which later forms part of the injection pore in the host membrane. Here we used labelling and crosslinking methods to show that\n                    <jats:styled-content style=\"fixed-case\">TCs<\/jats:styled-content>\n                    from a \u0394\n                    <jats:italic>ipaB<\/jats:italic>\n                    strain contain five\n                    <jats:styled-content style=\"fixed-case\">IpaD<\/jats:styled-content>\n                    subunits while the\n                    <jats:styled-content style=\"fixed-case\">TCs<\/jats:styled-content>\n                    from wild\u2010type can also contain one IpaB and four\n                    <jats:styled-content style=\"fixed-case\">IpaD<\/jats:styled-content>\n                    subunits. Electron microscopy followed by single particle and helical image analysis was used to reconstruct three\u2010dimensional images of\n                    <jats:styled-content style=\"fixed-case\">TCs<\/jats:styled-content>\n                    at \u223c20\u2009\u00c5 resolution. Docking of an IpaD crystal structure, constrained by the crosslinks observed, reveals that\n                    <jats:styled-content style=\"fixed-case\">TC<\/jats:styled-content>\n                    organisation is different from that of all previously proposed models. Our findings suggest new mechanisms for\n                    <jats:styled-content style=\"fixed-case\">TC<\/jats:styled-content>\n                    assembly and function. The\n                    <jats:styled-content style=\"fixed-case\">TC<\/jats:styled-content>\n                    is the only site within these secretion systems targeted by disease\u2010protecting antibodies. By suggesting how these act, our work will allow improvement of prophylactic and therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1111\/mmi.12843","type":"journal-article","created":{"date-parts":[[2014,10,29]],"date-time":"2014-10-29T05:31:32Z","timestamp":1414560692000},"page":"31-50","source":"Crossref","is-referenced-by-count":49,"title":["Three\u2010dimensional electron microscopy reconstruction and cysteine\u2010mediated crosslinking provide a model of the type\n                    <scp>III<\/scp>\n                    secretion system needle tip complex"],"prefix":"10.1111","volume":"95","author":[{"given":"Martin","family":"Cheung","sequence":"first","affiliation":[{"name":"Schools of Cellular &amp; Molecular Medicine and Biochemistry University of Bristol  Bristol BS8\u20091TD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da\u2010Kang","family":"Shen","sequence":"additional","affiliation":[{"name":"Schools of Cellular &amp; Molecular Medicine and Biochemistry University of Bristol  Bristol BS8\u20091TD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiaki","family":"Makino","sequence":"additional","affiliation":[{"name":"Graduate School of Frontier Biosciences University of Osaka  Osaka 565\u20100871 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Kato","sequence":"additional","affiliation":[{"name":"Graduate School of Frontier Biosciences University of Osaka  Osaka 565\u20100871 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Dorothea","family":"Roehrich","sequence":"additional","affiliation":[{"name":"Schools of Cellular &amp; Molecular Medicine and Biochemistry University of Bristol  Bristol BS8\u20091TD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Martinez\u2010Argudo","sequence":"additional","affiliation":[{"name":"Schools of Cellular &amp; Molecular Medicine and Biochemistry University of Bristol  Bristol BS8\u20091TD UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew L.","family":"Walker","sequence":"additional","affiliation":[{"name":"MLW Electron Microscopy Consulting Launceston  Cornwall PL15\u20099BB UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Murillo","sequence":"additional","affiliation":[{"name":"Schools of Cellular &amp; Molecular Medicine and Biochemistry University of Bristol  Bristol BS8\u20091TD 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