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G-104 The Helicobacter pylori adhesin protein HopQ exploits the dimer interface of human CEACAMs for oncoprotein translocation

Bonsor, Daniel, A.*; Zhao, Qing; Schmidinger, Barbara; Weiss, Evelyn; Wang, Jingheng; Deredge, Daniel§; Beadenkopf, Robert*; Dow, Blaine*; Fischer, Wolfgang; Beckett, Dorothy; Wintrode, Patrick, L.§; Haas, Rainer*,‖; Sundberg, Eric, J.*,¶,#,**

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2018 - Volume 77 - Issue - p 45
doi: 10.1097/01.qai.0000532617.80271.6c
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Helicobacter pylori infects half of the world's population and strains that encode the cag type IV secretion system for injection of the oncoprotein CagA into host gastric epithelial cells are associated with elevated levels of cancer. CagA translocation into host cells is dependent on interactions between the H. pylori adhesin protein HopQ and human CEACAMs. Here, we present high-resolution structures of numerous HopQ-CEACAM complexes and CEACAMs in their monomeric and dimeric forms establishing that HopQ uses a coupled folding and binding mechanism to engage the canonical CEACAM dimerization interface for CEACAM recognition. By combining mutagenesis with biophysical and functional analyses, we show that the modes of CEACAM recognition by HopQ and CEACAMs themselves are starkly different. Our data describe precise molecular mechanisms by which microbes exploit host CEACAMs for infection and enable future development of novel oncoprotein translocation inhibitors and H. pylori-specific antimicrobial agents.

*Institute of Human Virology, University of Maryland School of Medicine, University of Maryland, Baltimore

Max von Pettenkofer-Institut für Medizinische Mikrobiologie und Krankenhaushygiene, Ludwig-Maximilians-Universität, Pettenkoferstraβe 9a, München, Germany

Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland

§Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore

German Center for infection Research (DZIF), partner site LMU, München, Germany

Department of Medicine, University of Maryland School of Medicine, University of Maryland, Baltimore

#Department of Microbiology and Immunology, University of Maryland School of Medicine, University of Maryland, Baltimore

Corresponding author: esundberg@ihv.umaryland.edu

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