Haemolysin coregulated protein is an exported receptor and chaperone of type VI secretion substrates

Mol Cell. 2013 Sep 12;51(5):584-93. doi: 10.1016/j.molcel.2013.07.025. Epub 2013 Aug 15.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidohydrolases / metabolism
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Bacterial Secretion Systems / physiology*
  • Hemolysin Proteins / chemistry
  • Hemolysin Proteins / genetics
  • Hemolysin Proteins / metabolism*
  • Models, Molecular
  • Molecular Chaperones / metabolism
  • Muramidase / metabolism
  • Mutation
  • Protein Conformation
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / metabolism*
  • Substrate Specificity


  • Bacterial Proteins
  • Bacterial Secretion Systems
  • Hemolysin Proteins
  • Molecular Chaperones
  • Muramidase
  • Amidohydrolases
  • amidase