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

Nature Structural Biology volume 2, pages 154–162 (1995)Cite this article

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

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Authors and Affiliations

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

    Paul D. Adams, Isaiah T. Arkin & Donald M. Engelman

  2. Department of Cell Biology, Yale University, New Haven, Connecticut, 06520, USA

    Isaiah T. Arkin

  3. The Howard Hughes Medical Institute and Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, 06520, USA

    Axel T. Brünger

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  1. Paul D. Adams
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  2. Isaiah T. Arkin
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  3. Donald M. Engelman
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  4. Axel T. Brünger
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Adams, P., Arkin, I., Engelman, D. et al. Computational searching and mutagenesis suggest a structure for the pentameric transmembrane domain of phospholamban. Nat Struct Mol Biol 2, 154–162 (1995). https://doi.org/10.1038/nsb0295-154

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