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 α-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 ARG27 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.
authors: Department of Computational Biophysics and Bioinformatics, Faculty of Biotechnology, Biochemistry and Biophysics, Jagiellonian University, Gronostajowa 7, Poland.
authors: Adam
authors: A
authors: Orłowski
authors: Jean-François
authors: JF
authors: St-Pierre
authors: Aniket
authors: A
authors: Magarkar
authors: Alex
authors: A
authors: Bunker
authors: Marta
authors: M
authors: Pasenkiewicz-Gierula
authors: Ilpo
authors: I
authors: Vattulainen
authors: Tomasz
authors: T
authors: Róg
mesh_terms: D002394:Catechol O-Methyltransferase / Q000737:chemistry / Q000378:metabolism*; D030562:Databases, Protein; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017433:Protein Structure, Secondary
chemical_list: D008051:Lipid Bilayers; D002394:Catechol O-Methyltransferase