This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Domene, C. Articles by Vénien-Bryan, C. Search for Related Content PubMed PubMed Citation Articles by Domene, C. Articles by Vénien-Bryan, C.

Modeling of an Ion Channel in Its Open Conformation

Carmen Domene ^*, Declan A. Doyle  and Catherine Vénien-Bryan 

^* Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, Oxford OX1 3QZ, United Kingdom; Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom; and Structural Genomics Consortium, University of Oxford, Botnar Research Centre, Oxford OX3 7LD, United Kingdom

Correspondence: Address reprint requests and inquiries to Dr. Carmen Domene, E-mail: carmen.domene{at}chem.ox.ac.uk.

We have modeled the structure of KirBac1.1 in an open state using as a starting point the structure of KirBac1.1 in its closed conformation (Protein Data Bank 1P7B). To test the validity of the open-state model, molecular dynamics simulations in octane, a lipid bilayer mimetic, were carried out. Simulations of the closed conformer were used for comparison purposes. The total simulation time was 138 ns. The initial open model was refined by using projection maps obtained from electron microscopy experiments on two-dimensional crystals of the inwardly rectifying K+ channel KirBac3.1 from Magentospirillum magnetotacticum captured in its open state (C. Vénien-Bryan, unpublished data). Significant movements of the outer helices take place in going from the closed to the open model in agreement with structural and biochemical data in potassium channels, which suggests that gating is accomplished by a conformational change that takes place in the transmembrane domain upon an external stimulus. The motion of the inner helices is mainly achieved by bending at conserved glycine residues that have been previously reported to act as molecular hinges. Overall, these simulations suggest that the open conformer is stable, providing a plausible all-atom model that will enable the study of potential gating mechanisms in more detail.

This article has been cited by other articles:

				S. Vemparala, C. Domene, and M. L. Klein Interaction of Anesthetics with Open and Closed Conformations of a Potassium Channel Studied via Molecular Dynamics and Normal Mode Analysis Biophys. J., June 1, 2008; 94(11): 4260 - 4269. [Abstract] [Full Text] [PDF]

				S. J. Tucker and T. Baukrowitz How Highly Charged Anionic Lipids Bind and Regulate Ion Channels J. Gen. Physiol., April 28, 2008; 131(5): 431 - 438. [Full Text] [PDF]

				A. Rosenhouse-Dantsker and D. E. Logothetis New Roles for a Key Glycine and Its Neighboring Residue in Potassium Channel Gating Biophys. J., October 15, 2006; 91(8): 2860 - 2873. [Abstract] [Full Text] [PDF]

				C. Domene, S. Vemparala, M. L. Klein, C. Venien-Bryan, and D. A. Doyle Role of Aromatic Localization in the Gating Process of a Potassium Channel Biophys. J., January 1, 2006; 90(1): L01 - L03. [Abstract] [Full Text] [PDF]

				S. Ding, L. Ingleby, C. A. Ahern, and R. Horn Investigating the Putative Glycine Hinge in Shaker Potassium Channel J. Gen. Physiol., August 29, 2005; 126(3): 213 - 226. [Abstract] [Full Text] [PDF]