A leucine zipper stabilizes the pentameric membrane domain of phospholamban and forms a coiled-coil pore structure

Heather K.B. Simmerman, Yvonne M. Kobayashi, Joseph M. Autry, Larry R. Jones

Research output: Contribution to journalArticle

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Abstract

Phospholamban is a phosphoprotein regulator of cardiac sarcoplasmic reticulum which is phosphorylated in response to β-adrenergic stimulation. Previous results have shown that phospholamban forms Ca2+-selective channels in lipid bilayers. The channel-forming domain has been localized to amino acid residues 26-52, which form a stable pentameric, helical structure. The specific residues responsible for stabilizing the pentameric membrane domain of phospholamban have been identified by mutational analysis. Residues 26-52 were individually mutated to Ala or Phe, and the ability of the resulting mutant to form a pentamer or other oligomer was assessed by SDS- polyacrylamide gel electrophoresis analysis. Replacement of Leu37, Ile40, Leu44, Ile47, or Leu51 by Ala prevented pentamer formation, indicating their essential involvement in the oligomeric assembly. The heptad repeats, and 3-4-residue spacing of the essential amino acids suggest that residues 37-52 adopt a pentameric coiled-coil structure stabilized by a leucine zipper motif formed by the close packing of Leu37, Ile40, Leu44, Ile47, and Leu51. The resulting symmetric structure contains a central pore defined by the hydrophobic surface of the five stabilizing leucine zippers, which are oriented to the interior and form the backbone of the pentamer.

Original languageEnglish (US)
Pages (from-to)5941-5946
Number of pages6
JournalJournal of Biological Chemistry
Volume271
Issue number10
DOIs
StatePublished - Mar 8 1996

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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