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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 (Dimer structure shown in Blue/Green) is a small (18.4 kDa) non-secreted bacterial co-chaperone that binds to this translocator proteins.
PcrH crystal structure has been solved carrying a homologous sequence that is present in these translocator proteins. 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. In this case, PcrH from Pseudomonas Aeruginosa consist of three . The first Tpr motif is represented in red, the second in green and the third in cyan color, also an additional alpha-helix is represented in blue. 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.
