The structure of phospholamban pentamer reveals a channel-like architecture in membranes

Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):10870-5. doi: 10.1073/pnas.0504920102. Epub 2005 Jul 25.


Contraction and relaxation of heart muscle cells is regulated by cycling of calcium between cytoplasm and sarcoplasmic reticulum. Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. Since PLN was discovered approximately 30 years ago, extensive studies have aimed to explain how it influences calcium pumps and to determine whether it acts as an ion channel. We have determined by solution NMR methods the atomic resolution structure of an unphosphorylated PLN pentamer in dodecylphosphocholine micelles. The unusual bellflower-like assembly is held together by leucine/isoleucine zipper motifs along the membrane-spanning helices. The structure reveals a channel-forming architecture that could allow passage of small ions. The central pore gradually widens toward the cytoplasmic end as the transmembrane helices twist around each other and bend outward. The dynamic N-terminal amphipathic helices point away from the membrane, perhaps facilitating recognition and inhibition of the calcium pump.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Calcium-Binding Proteins / chemistry*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Calcium-Transporting ATPases / chemistry
  • Calcium-Transporting ATPases / metabolism
  • Humans
  • In Vitro Techniques
  • Ion Channels / chemistry
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Structure, Quaternary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sarcoplasmic Reticulum / metabolism
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases


  • Calcium-Binding Proteins
  • Ion Channels
  • Recombinant Fusion Proteins
  • phospholamban
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Calcium-Transporting ATPases

Associated data

  • PDB/1ZLL