Molecular Playground/Pcr H
From Proteopedia
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Revision as of 19:51, 17 December 2012
One of the CBI Molecules being studied in the University of Massachusetts Amherst Chemistry-Biology Interface Program at UMass Amherst and on display at the Molecular Playground
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PcrH
Many Gram-negative pathogens use a Type III secretion (T3S) system to inject effector proteins into the cytoplasm of their target cell. These effectors need to translocate through the plasma membrane, presumably through a proteinaceous structure, the translocon. Substantial genetic and biochemical data indicate the translocon is composed by two T3S proteins, in the case of Pseudomonas aeruginosa, the translocators protein are PopB and PopD. Since PopB and PopD can bind to lipid bilayers and form pores in them, they need to be maintained in a state competent for secretion and also not toxic for the bacterial cell. PrcH is a small (18.4 kDa) non-secreted bacterial co-chaperone responsible for this (Dimer structure shown in Blue/Green).
PcrH binds to a VELNAP present in both PopB and PopD (9 residue peptide (Pink) shown bound to Chain A in structure (Blue)). PcrH's characteristic fold is composed of Tetratricopeptide Repeats (TPR repeats). TPR repeats consist of a 34 amino-acid sequence motif that folds into two antiparallel alpha-helices that serve as interaction modules and multi-protein complex mediators. This fold is also present in Eukaryotic co-chaperons such as HOP(Heat shock protein Organizing Protein). The VELNAP sequence motif binding is displayed as three hydrophobic pockets in the concave side of the TPR domain receive three hydrophobic residues within the CBM present in the synthetic peptide. This interaction keeps them in a metastable non oligomeric state in the cytosol, thus protecting them from degradation and aggregation. It is also believed that PcrH has an active role in delivering PopB and PopD to the basal body of the T3S system, where an ATPse unfolds and secretes the translocators PopB and PopD.
Given its key role in molecular pathogenesis PcrH is a potential target for drug design.
Proteopedia Page Contributors and Editors (what is this?)
Carolina Morell-Perez, Yuzhou Tang, Michal Harel, Fabian Romano, Alexander Berchansky, Luis E Ramirez-Tapia
