Properties of the Membrane Binding Component of Catechol-O-methyltransferase Revealed by Atomistic Molecular Dynamics Simulations

A. Orlowski, J. F. St-Pierre, A. Magarkar, A. Bunker, M. Pasenkiewicz-Gierula, I. Vattulainen, T. Rog

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

We used atomistic simulations to study the membrane-bound form of catechol-O-methyltransferase (MB-COMT). In particular we investigated the 26-residue transmembrane a-helical segment of MB-COMT together with the 24-residue fragment that links the transmembrane component to the main protein unit that was not included in our model. In numerous independent simulations we observed the formation of a salt bridge between ARC 27 and GLU40. The salt bridge closed the flexible loop that formed in the linker and kept it in the vicinity of the membrane-water interface. All simulations supported this conclusion that the linker has a clear affinity for the interface and preferentially arranges its residues to reside next to the membrane, without a tendency to relocate into the water phase. Furthermore, an extensive analysis of databases for sequences of membrane proteins that have a single transmembrane helical segment brought about an interesting view that the flexible loop observed in our work can be a common structural element in these types of proteins. In the same spirit we close the article by discussing the role of salt bridges in the formation of three-dimensional structures of membrane proteins that exhibit a single transmembrane helix.
Original languageEnglish
JournalJournal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical
Volume115
Issue number46
Pages (from-to)13541-13550
Number of pages10
ISSN1520-6106
DOIs
Publication statusPublished - 2011

Cite this

Orlowski, A. ; St-Pierre, J. F. ; Magarkar, A. ; Bunker, A. ; Pasenkiewicz-Gierula, M. ; Vattulainen, I. ; Rog, T. / Properties of the Membrane Binding Component of Catechol-O-methyltransferase Revealed by Atomistic Molecular Dynamics Simulations. In: Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical. 2011 ; Vol. 115, No. 46. pp. 13541-13550.
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title = "Properties of the Membrane Binding Component of Catechol-O-methyltransferase Revealed by Atomistic Molecular Dynamics Simulations",
abstract = "We used atomistic simulations to study the membrane-bound form of catechol-O-methyltransferase (MB-COMT). In particular we investigated the 26-residue transmembrane a-helical segment of MB-COMT together with the 24-residue fragment that links the transmembrane component to the main protein unit that was not included in our model. In numerous independent simulations we observed the formation of a salt bridge between ARC 27 and GLU40. The salt bridge closed the flexible loop that formed in the linker and kept it in the vicinity of the membrane-water interface. All simulations supported this conclusion that the linker has a clear affinity for the interface and preferentially arranges its residues to reside next to the membrane, without a tendency to relocate into the water phase. Furthermore, an extensive analysis of databases for sequences of membrane proteins that have a single transmembrane helical segment brought about an interesting view that the flexible loop observed in our work can be a common structural element in these types of proteins. In the same spirit we close the article by discussing the role of salt bridges in the formation of three-dimensional structures of membrane proteins that exhibit a single transmembrane helix.",
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Properties of the Membrane Binding Component of Catechol-O-methyltransferase Revealed by Atomistic Molecular Dynamics Simulations. / Orlowski, A.; St-Pierre, J. F.; Magarkar, A.; Bunker, A.; Pasenkiewicz-Gierula, M.; Vattulainen, I.; Rog, T.

In: Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical, Vol. 115, No. 46, 2011, p. 13541-13550.

Research output: Contribution to journalJournal articleResearchpeer-review

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T1 - Properties of the Membrane Binding Component of Catechol-O-methyltransferase Revealed by Atomistic Molecular Dynamics Simulations

AU - Orlowski, A.

AU - St-Pierre, J. F.

AU - Magarkar, A.

AU - Bunker, A.

AU - Pasenkiewicz-Gierula, M.

AU - Vattulainen, I.

AU - Rog, T.

PY - 2011

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AB - We used atomistic simulations to study the membrane-bound form of catechol-O-methyltransferase (MB-COMT). In particular we investigated the 26-residue transmembrane a-helical segment of MB-COMT together with the 24-residue fragment that links the transmembrane component to the main protein unit that was not included in our model. In numerous independent simulations we observed the formation of a salt bridge between ARC 27 and GLU40. The salt bridge closed the flexible loop that formed in the linker and kept it in the vicinity of the membrane-water interface. All simulations supported this conclusion that the linker has a clear affinity for the interface and preferentially arranges its residues to reside next to the membrane, without a tendency to relocate into the water phase. Furthermore, an extensive analysis of databases for sequences of membrane proteins that have a single transmembrane helical segment brought about an interesting view that the flexible loop observed in our work can be a common structural element in these types of proteins. In the same spirit we close the article by discussing the role of salt bridges in the formation of three-dimensional structures of membrane proteins that exhibit a single transmembrane helix.

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JO - Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical

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