Architecture of the human erythrocyte ankyrin-1 complex

  • Nat Struct Mol Biol. 2022 Jul;29(7):706-718. doi: 10.1038/s41594-022-00792-w.
Francesca Vallese  1  2  3 ,  Kookjoo Kim  1  2  3 ,  Laura Y Yen  2 ,  Jake D Johnston  2  4 ,  Alex J Noble  4 ,  Tito Calì  5  6  7 ,  Oliver Biggs Clarke  8  9  10
Affiliations
  • 1. Department of Anesthesiology, Columbia University Irving Medical Center, New York, NY, USA.
  • 2. Department of Physiology and Cellular Biophysics, Columbia University, New York, NY, USA.
  • 3. Irving Institute for Clinical and Translational Research, Columbia University, New York, NY, USA.
  • 4. Simons Electron Microscopy Center, New York Structural Biology Center, New York, NY, USA.
  • 5. Department of Biomedical Sciences, University of Padua, Padua, Italy.
  • 6. Padua Neuroscience Center (PNC), University of Padua, Padua, Italy.
  • 7. Study Center for Neurodegeneration (CESNE), University of Padua, Padua, Italy.
  • 8. Department of Anesthesiology, Columbia University Irving Medical Center, New York, NY, USA. [email protected].
  • 9. Department of Physiology and Cellular Biophysics, Columbia University, New York, NY, USA. [email protected].
  • 10. Irving Institute for Clinical and Translational Research, Columbia University, New York, NY, USA. [email protected].
PMID: 35835865 DOI: 10.1038/s41594-022-00792-w
Abstract

The stability and shape of the erythrocyte membrane is provided by the ankyrin-1 complex, but how it tethers the spectrin-actin Cytoskeleton to the lipid bilayer and the nature of its association with the band 3 anion exchanger and the Rhesus glycoproteins remains unknown. Here we present structures of ankyrin-1 complexes purified from human erythrocytes. We reveal the architecture of a core complex of ankyrin-1, the Rhesus proteins RhAG and RhCE, the band 3 anion exchanger, protein 4.2, glycophorin A and glycophorin B. The distinct T-shaped conformation of membrane-bound ankyrin-1 facilitates recognition of RhCE and, unexpectedly, the water channel aquaporin-1. Together, our results uncover the molecular details of ankyrin-1 association with the erythrocyte membrane, and illustrate the mechanism of ankyrin-mediated membrane protein clustering.