Crystallographic analysis of the Sec-dependent secretion chaperone CsaA.

The eubacterial protein CsaA has been proposed to act as a protein secretion chaperone in the Sec-dependent translocation pathway. Two structures of CsaA from Bacillus subtilis were solved by X-ray crystallography and refined to 1.9 and 2.0 Å resolution. Structural analysis revealed two potential substrate binding pockets on the surface of CsaA. These pockets display biochemical properties consistent with the substrate binding preference of CsaA. A structure of CsaA from Agrobacterium tumefaciens in complex with a phage display derived peptide was solved to 1.65Å resolution. The peptide binds to the substrate binding pocket on the surface of CsaA. Three residues of the bound peptide form specific interactions with CsaA: glutamine at position (-6) and small hydrophobic residues at positions (-5) and (-3). A conserved arginine residue in the binding site of CsaA likely acts as a clamp that transiently interacts with and stabilizes the peptides in the binding site.