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

Abstract

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.

Catch bond drives stator mechanosensitivity in the bacterial flagellar motor

“…The N-terminal portion of MotB must perform a large conformational extension to reach the PG ( 38 , 39 ). Recently, a conformational change upon binding has also been hypothesized in the PG-associated C-terminal of the closely related Outer Membrane protein OmpA ( 46 ). These facts suggest a possible catch-bond mechanism in which tension across the PG–MotB C interface can promote either conformational rearrangements or a positional shift of the PGB within the PGB pocket which lead to further exposure of binding residues to the PG, increasing the strength of the bond and the lifetime of the stator unit within the BFM complex (as sketched in Fig.…”

The Mutation of Conservative Asp268 Residue in the Peptidoglycan-Associated Domain of the OmpA Protein Affects Multiple Acinetobacter baumannii Virulence Characteristics

“…The interaction between the periplasmic domain of OmpA and peptidoglycan suggests that OmpA plays a role in the integrity of the bacterial surface [15]. Moreover, in a number of Gram-negative bacteria—including A. baumannii —the OmpA dimerization via its C-terminus has been demonstrated [13,32,33]. It is thought that dimerization stabilizes the overall structure of OmpA by preventing the collapse of the flexible linker between the β-barrel and periplasmic domains [34].…”

A catch-bond drives stator mechanosensitivity in the Bacterial Flagellar Motor

“…57 Recently, a conformational change upon binding has also been hypothesized in the PG-associated C-terminal of the closely related Outer Membrane protein OmpA. 58 These facts suggest a possible catch-bond mechanism in which tension across the PG-MotB C interface can promote the conformational rearrangements which lead to further exposure of binding residues to the PG, increasing the strength of the bond and the lifetime of the stator within the BFM complex (as sketched in Fig. 4).…”