Computational searching and mutagenesis suggest a structure for the pentameric transmembrane domain of phospholamban

P D Adams; I T Arkin; D M Engelman; A T Brünger

doi:10.1038/nsb0295-154

Computational searching and mutagenesis suggest a structure for the pentameric transmembrane domain of phospholamban

Nat Struct Biol. 1995 Feb;2(2):154-62. doi: 10.1038/nsb0295-154.

Authors

P D Adams¹, I T Arkin, D M Engelman, A T Brünger

Affiliation

¹ Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.

PMID: 7749920
DOI: 10.1038/nsb0295-154

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Amino Acid Sequence
Calcium-Binding Proteins / chemistry*
Computer Simulation*
Membrane Proteins / chemistry*
Models, Molecular*
Molecular Sequence Data
Mutagenesis
Protein Structure, Secondary
Protein Structure, Tertiary*
Recombinant Fusion Proteins / chemistry

Substances

Calcium-Binding Proteins
Membrane Proteins
Recombinant Fusion Proteins
phospholamban