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

Paul D. Adams; Isaiah T. Arkin; Donald M. Engelman; Axel T. Brünger

doi:10.1038/nsb0295-154

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

Paul D. Adams, Isaiah T. Arkin, Donald M. Engelman, Axel T. Brünger

Research output: Contribution to journal › Article › peer-review

196 Scopus citations

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 a-helices with a well-defined channel, lined solely by hydrophobic residues.

Original language	English
Pages (from-to)	154-162
Number of pages	9
Journal	Nature Structural Biology
Volume	2
Issue number	2
DOIs	https://doi.org/10.1038/nsb0295-154
State	Published - Feb 1995
Externally published	Yes

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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 a-helices with a well-defined channel, lined solely by hydrophobic residues.",

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

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