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

ABSTRACT: 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.

SUBMITTER: Silverman JM

PROVIDER: S-EPMC3844553 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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

Silverman Julie M JM Agnello Danielle M DM Zheng Hongjin H Andrews Benjamin T BT Li Mo M Catalano Carlos E CE Gonen Tamir T Mougous Joseph D JD

Molecular cell 20130815 5

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. ...[more]

PMID: 23954347

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Project description:The bacterium Proteus mirabilis can communicate identity through the secretion of the self-identity protein IdsD via the type VI secretion (T6S) system. IdsD secretion is essential for self-versus-nonself recognition behaviors in these populations. Here we provide an answer to the unresolved question of how the activity of a T6S substrate, such as IdsD, is regulated before secretion. We demonstrate that IdsD is found in clusters that form independently of the T6S machinery and activity. We show that the IdsC protein, which is a member of the proposed DUF4123 chaperone family, is essential for the maintenance of these clusters and of the IdsD protein itself. We provide evidence that amino acid disruptions in IdsC are sufficient to disrupt IdsD secretion but not IdsD localization into subcellular clusters, strongly supporting the notion that IdsC functions in at least two different ways: maintaining IdsD levels and secreting IdsD. We propose that IdsC, and likely other DUF4123-containing proteins, functions to regulate T6S substrates in the donor cell both by maintaining protein levels and by mediating secretion at the T6S machinery.IMPORTANCE Understanding the subcellular dynamics of self-identity proteins is crucial for developing models of self-versus-nonself recognition. We directly addressed how a bacterium restricts self-identity information before cell-cell exchange. We resolved two conflicting models for type VI secretion (T6S) substrate regulation by focusing on the self-identity protein IdsD. One model is that a cognate immunity protein binds the substrate, inhibiting activity before transport. Another model proposes that DUF4123 proteins act as chaperones in the donor cell, but no detailed molecular mechanism was previously known. We resolve this discrepancy and propose a model wherein a chaperone couples IdsD sequestration with its localization. Such a molecular mechanism restricts the communication of identity, and possibly other T6S substrates, in producing cells.

Dataset Information

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

Publications

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

Similar Datasets

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