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Title: Insights into PG-binding, conformational change, and dimerization of the OmpA C-terminal domains from Salmonella enterica serovar Typhimurium and Borrelia burgdorferi: Characterization of OmpA C-Terminal Domain

Abstract

S. 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 b-barrel trans membrane domain and a C-terminal domain (OmpACTD). The OmpACTD 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 OmpACTD from two pathogens: S. Typhimurium (STOmpACTD) in open and closed forms and causative agent of Lyme Disease Borrelia burgdorferi (BbOmpACTD), in closed form. In the open form of STOmpACTD, an aspartic acid residue from a long b2-a3 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 STOmpACTD and in the structure of BbOmpACTD, a sulfate group from the crystallization buffer is tightly bound at the binding site. The differences between the closed and open forms of STOmpACTD, suggest a large conformational change that includes an extension of a3 helix by orderingmore » a part of b2-a3 loop. We propose that the sulfate anion observed in these structures mimics the carboxylate group of PG when bound to STOmpACTD suggesting PG-anchoring mechanism. In addition, the binding of PG or a ligand mimic may enhance dimerization of STOmpACTD, or possibly that of full length STOmpA.« less

Authors:
 [1];  [2];  [3];  [3];  [3];  [3];  [4];  [5];  [5];  [6];  [1]
  1. Center for Structural Genomics of Infectious Diseases, University of Chicago, 5735 South Ellis Avenue Chicago Illinois 60637; Midwest Center for Structural Genomics, Argonne National Laboratory, Argonne Illinois 60439; Structural Biology Center, Biosciences, Argonne National Laboratory, Argonne Illinois 60439
  2. National Security Directorate, Pacific Northwest National Laboratory, Richland Washington 99352
  3. Midwest Center for Structural Genomics, Argonne National Laboratory, Argonne Illinois 60439
  4. Center for Structural Genomics of Infectious Diseases, University of Chicago, 5735 South Ellis Avenue Chicago Illinois 60637
  5. Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland Washington 99352
  6. Center for Structural Genomics of Infectious Diseases, University of Chicago, 5735 South Ellis Avenue Chicago Illinois 60637; Midwest Center for Structural Genomics, Argonne National Laboratory, Argonne Illinois 60439
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
OSTI Identifier:
1398993
DOE Contract Number:  
AC02-06CH11357
Resource Type:
Journal Article
Journal Name:
Protein Science
Additional Journal Information:
Journal Volume: 26; Journal Issue: 9; Journal ID: ISSN 0961-8368
Publisher:
The Protein Society
Country of Publication:
United States
Language:
English
Subject:
OmpA C-terminal domain (OmpACTD); OmpACTD -like domain; Outer membrane protein A (OmpA); PG-binding; conformational change; dimerization; peptidoglycan (PG)

Citation Formats

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, and Joachimiak, Andrzej. Insights into PG-binding, conformational change, and dimerization of the OmpA C-terminal domains from Salmonella enterica serovar Typhimurium and Borrelia burgdorferi: Characterization of OmpA C-Terminal Domain. United States: N. p., 2017. Web. doi:10.1002/pro.3209.
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. Insights into PG-binding, conformational change, and dimerization of the OmpA C-terminal domains from Salmonella enterica serovar Typhimurium and Borrelia burgdorferi: Characterization of OmpA C-Terminal Domain. United States. doi:10.1002/pro.3209.
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, and Joachimiak, Andrzej. Mon . "Insights into PG-binding, conformational change, and dimerization of the OmpA C-terminal domains from Salmonella enterica serovar Typhimurium and Borrelia burgdorferi: Characterization of OmpA C-Terminal Domain". United States. doi:10.1002/pro.3209.
@article{osti_1398993,
title = {Insights into PG-binding, conformational change, and dimerization of the OmpA C-terminal domains from Salmonella enterica serovar Typhimurium and Borrelia burgdorferi: Characterization of OmpA C-Terminal Domain},
author = {Tan, Kemin and Deatherage Kaiser, Brooke L. and Wu, Ruiying and Cuff, Marianne and Fan, Yao and Bigelow, Lance and Jedrzejczak, Robert P. and Adkins, Joshua N. and Cort, John R. and Babnigg, Gyorgy and Joachimiak, Andrzej},
abstractNote = {S. 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 b-barrel trans membrane domain and a C-terminal domain (OmpACTD). The OmpACTD 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 OmpACTD from two pathogens: S. Typhimurium (STOmpACTD) in open and closed forms and causative agent of Lyme Disease Borrelia burgdorferi (BbOmpACTD), in closed form. In the open form of STOmpACTD, an aspartic acid residue from a long b2-a3 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 STOmpACTD and in the structure of BbOmpACTD, a sulfate group from the crystallization buffer is tightly bound at the binding site. The differences between the closed and open forms of STOmpACTD, suggest a large conformational change that includes an extension of a3 helix by ordering a part of b2-a3 loop. We propose that the sulfate anion observed in these structures mimics the carboxylate group of PG when bound to STOmpACTD suggesting PG-anchoring mechanism. In addition, the binding of PG or a ligand mimic may enhance dimerization of STOmpACTD, or possibly that of full length STOmpA.},
doi = {10.1002/pro.3209},
journal = {Protein Science},
issn = {0961-8368},
number = 9,
volume = 26,
place = {United States},
year = {2017},
month = {6}
}

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