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. Epub 2022 Jul 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Anion Exchange Protein 1, Erythrocyte* / analysis
  • Anion Exchange Protein 1, Erythrocyte* / chemistry
  • Anion Exchange Protein 1, Erythrocyte* / metabolism
  • Ankyrins* / metabolism
  • Cytoskeletal Proteins / metabolism
  • Erythrocyte Membrane / chemistry
  • Erythrocyte Membrane / metabolism
  • Erythrocytes / metabolism
  • Humans
  • Spectrin


  • Anion Exchange Protein 1, Erythrocyte
  • Ankyrins
  • Cytoskeletal Proteins
  • Spectrin