Insights into PG-binding, conformational change, and dimerization of the OmpA C-terminal domains from Salmonella enterica serovar Typhimurium and Borrelia burgdorferi.

Salmonella enterica serovar Typhimurium can induce both humoral and cell-mediated responses when establishing itself in the host. These responses are primarily stimulated against the lipopolysaccharide and major outer membrane (OM) proteins. OmpA is one of these major OM proteins. It comprises a N-terminal eight-stranded β-barrel transmembrane domain and a C-terminal domain (OmpA ). The OmpA and its homologs are believed to bind to peptidoglycan (PG) within the periplasm, maintaining bacterial osmotic homeostasis and modulating the permeability and integrity of the OM. Here we present the first crystal structures of the OmpA from two pathogens: S. typhimurium (STOmpA ) in open and closed forms and causative agent of Lyme Disease Borrelia burgdorferi (BbOmpA ), in closed form. In the open form of STOmpA , an aspartate residue from a long β2-α3 loop points into the binding pocket, suggesting that an anion group such as a carboxylate group from PG is favored at the binding site. In the closed form of STOmpA and in the structure of BbOmpA , a sulfate group from the crystallization buffer is tightly bound at the binding site. The differences between the closed and open forms of STOmpA , suggest a large conformational change that includes an extension of α3 helix by ordering a part of β2-α3 loop. We propose that the sulfate anion observed in these structures mimics the carboxylate group of PG when bound to STOmpA suggesting PG-anchoring mechanism. In addition, the binding of PG or a ligand mimic may enhance dimerization of STOmpA , or possibly that of full length STOmpA.