Computational searching and mutagenesis suggest a structure for the pentameric transmembrane domain of phospholamban.
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.
Adams
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PD
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.
Arkin
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IT
Engelman
D M
DM
Brünger
A T
AT
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
D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D000099211:Phospholamban