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Insights into PG‐binding, conformational change, and dimerization of the OmpA C‐terminal domains from Salmonella enterica serovar Typhimurium and Borrelia burgdorferi
Author(s) -
Tan Kemin,
Deatherage Kaiser Brooke L.,
Wu Ruiying,
Cuff Marianne,
Fan Yao,
Bigelow Lance,
Jedrzejczak Robert P.,
Adkins Joshua N.,
Cort John R.,
Babnigg Gyorgy,
Joachimiak Andrzej
Publication year - 2017
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.3209
Subject(s) - periplasmic space , borrelia burgdorferi , conformational change , biology , bacterial outer membrane , binding site , protein structure , salmonella enterica , transmembrane domain , biochemistry , peptidoglycan , chemistry , microbiology and biotechnology , biophysics , escherichia coli , cell wall , membrane , antibody , immunology , gene
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 CTD ). The OmpA CTD 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 CTD from two pathogens: S. typhimurium ( S TOmpA CTD ) in open and closed forms and causative agent of Lyme Disease Borrelia burgdorferi ( Bb OmpA CTD ), in closed form. In the open form of S TOmpA CTD , 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 S TOmpA CTD and in the structure of Bb OmpA CTD , a sulfate group from the crystallization buffer is tightly bound at the binding site. The differences between the closed and open forms of S TOmpA CTD , 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 S TOmpA CTD suggesting PG‐anchoring mechanism. In addition, the binding of PG or a ligand mimic may enhance dimerization of S TOmpA CTD , or possibly that of full length S TOmpA.