title: Computational searching and mutagenesis suggest a structure for the pentameric transmembrane domain of phospholamban.
abstract: Structural and environmental constraints greatly simplify the folding problem for membrane proteins. Computational methods can be used in a global search to find a small number of chemically reasonable models within these constraints, such that a modest set of experimental data can distinguish among them. We show that, for phospholamban, the global search can be further simplified by reducing the problem to two-body, rather than many-body, interactions. This method of a constrained global search combined with experimental mutagenesis data yields a three-dimensional structure for this pentameric ion channel. The model is a left-handed symmetric homopentamer of alpha-helices with a well-defined channel, lined solely by hydrophobic residues.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Adams
authors.forename: I T
authors.initials: IT
authors.lastname: Arkin
authors.forename: D M
authors.initials: DM
authors.lastname: Engelman
authors.forename: A T
authors.initials: AT
authors.lastname: Brünger
mesh_terms: D000595:Amino Acid Sequence; D002135:Calcium-Binding Proteins / Q000737:chemistry*; D003198:Computer Simulation; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D000099211:Phospholamban