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Full-length OmpA: structure, function, and membrane interactions predicted by molecular dynamics simulations

Full-length OmpA: structure, function, and membrane interactions predicted by molecular dynamics simulations
Full-length OmpA: structure, function, and membrane interactions predicted by molecular dynamics simulations
OmpA is a multidomain protein found in the outer membranes of most Gram-negative bacteria. Despite a wealth of reported structural and biophysical studies, the structure-function relationships of this protein remain unclear. For example, it is still debated whether it functions as a pore, and the precise molecular role it plays in attachment to the peptidoglycan of the periplasm is unknown. The absence of a consensus view is partly due to the lack of a complete structure of the full-length protein. To address this issue, we performed molecular-dynamics simulations of the full-length model of the OmpA dimer proposed by Robinson and co-workers. The N-terminal domains were embedded in an asymmetric model of the outer membrane, with lipopolysaccharide molecules in the outer leaflet and phospholipids in the inner leaflet. Our results reveal a large dimerization interface within the membrane environment, ensuring that the dimer is stable over the course of the simulations. The linker is flexible, expanding and contracting to pull the globular C-terminal domain up toward the membrane or push it down toward the periplasm, suggesting a possible mechanism for providing mechanical stability to the cell. The external loops were more stabilized than was observed in previous studies due to the extensive dimerization interface and presence of lipopolysaccharide molecules in our outer-membrane model, which may have functional consequences in terms of OmpA adhesion to host cells. In addition, the pore-gating behavior of the protein was modulated compared with previous observations, suggesting a possible role for dimerization in channel regulation.
0006-3495
1692-1702
Ortiz-Suarez, Maite L.
628671e0-e605-4a32-83de-35d16993591e
Samsudin, Mohd
b01e87a0-af50-44d6-bca4-f511c40165f9
Piggot, Thomas J.
d91247c8-1c4d-4cdb-a398-47546dfbe64a
Bond, Peter J.
08f46940-85e8-44c4-a368-d94342a10fd6
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394
Ortiz-Suarez, Maite L.
628671e0-e605-4a32-83de-35d16993591e
Samsudin, Mohd
b01e87a0-af50-44d6-bca4-f511c40165f9
Piggot, Thomas J.
d91247c8-1c4d-4cdb-a398-47546dfbe64a
Bond, Peter J.
08f46940-85e8-44c4-a368-d94342a10fd6
Khalid, Syma
90fbd954-7248-4f47-9525-4d6af9636394

Ortiz-Suarez, Maite L., Samsudin, Mohd, Piggot, Thomas J., Bond, Peter J. and Khalid, Syma (2016) Full-length OmpA: structure, function, and membrane interactions predicted by molecular dynamics simulations. Biophysical Journal, 111 (8), 1692-1702. (doi:10.1016/j.bpj.2016.09.009).

Record type: Article

Abstract

OmpA is a multidomain protein found in the outer membranes of most Gram-negative bacteria. Despite a wealth of reported structural and biophysical studies, the structure-function relationships of this protein remain unclear. For example, it is still debated whether it functions as a pore, and the precise molecular role it plays in attachment to the peptidoglycan of the periplasm is unknown. The absence of a consensus view is partly due to the lack of a complete structure of the full-length protein. To address this issue, we performed molecular-dynamics simulations of the full-length model of the OmpA dimer proposed by Robinson and co-workers. The N-terminal domains were embedded in an asymmetric model of the outer membrane, with lipopolysaccharide molecules in the outer leaflet and phospholipids in the inner leaflet. Our results reveal a large dimerization interface within the membrane environment, ensuring that the dimer is stable over the course of the simulations. The linker is flexible, expanding and contracting to pull the globular C-terminal domain up toward the membrane or push it down toward the periplasm, suggesting a possible mechanism for providing mechanical stability to the cell. The external loops were more stabilized than was observed in previous studies due to the extensive dimerization interface and presence of lipopolysaccharide molecules in our outer-membrane model, which may have functional consequences in terms of OmpA adhesion to host cells. In addition, the pore-gating behavior of the protein was modulated compared with previous observations, suggesting a possible role for dimerization in channel regulation.

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More information

Accepted/In Press date: 6 September 2016
e-pub ahead of print date: 18 October 2016
Organisations: Computational Systems Chemistry

Identifiers

Local EPrints ID: 401942
URI: http://eprints.soton.ac.uk/id/eprint/401942
ISSN: 0006-3495
PURE UUID: 58d20e71-def4-4db5-98a3-c25d52d9254e
ORCID for Mohd Samsudin: ORCID iD orcid.org/0000-0003-2766-4459
ORCID for Syma Khalid: ORCID iD orcid.org/0000-0002-3694-5044

Catalogue record

Date deposited: 25 Oct 2016 13:00
Last modified: 15 Mar 2024 03:29

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Contributors

Author: Maite L. Ortiz-Suarez
Author: Mohd Samsudin ORCID iD
Author: Thomas J. Piggot
Author: Peter J. Bond
Author: Syma Khalid ORCID iD

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