Haemolysin Coregulated Protein Is an Exported Receptor and Chaperone of Type VI Secretion Substrates

• DOI: 10.1016/j.molcel.2013.07.025
• Publication Date: 2013-08-15T17:39:30Z
• Authors: Julie M. Silverman; Danielle M. Agnello; Hongjin Zheng; Benjamin T. Andrews; Mo Li; Carlos E. Catalano; Tamir Gonen; Joseph D. Mougous
• Keywords: Models, Molecular; 0303 health sciences; Protein Conformation; Cell Biology; Amidohydrolases; Substrate Specificity; Hemolysin Proteins; 03 medical and health sciences; Bacterial Proteins; Mutation; Pseudomonas aeruginosa; Muramidase; Molecular Biology; Bacterial Secretion Systems; Molecular Chaperones

Secretion systems require high-fidelity mechanisms to discriminate substrates among the vast cytoplasmic pool of proteins. Factors mediating substrate recognition by the type VI secretion system (T6SS) of Gram-negative bacteria, a widespread pathway that translocates effector proteins into target bacterial cells, have not been defined. We report that haemolysin coregulated protein (Hcp), a ring-shaped hexamer secreted by all characterized T6SSs, binds specifically to cognate effector molecules. Electron microscopy analysis of an Hcp-effector complex from Pseudomonas aeruginosa revealed the effector bound to the inner surface of Hcp. Further studies demonstrated that interaction with the Hcp pore is a general requirement for secretion of diverse effectors encompassing several enzymatic classes. Though previous models depict Hcp as a static conduit, our data indicate it is a chaperone and receptor of substrates. These unique functions of a secreted protein highlight fundamental differences between the export mechanism of T6 and other characterized secretory pathways.