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CCeMMP Seminar Series – A/Prof. Oliver Clarke March 2022

Architecture of the erythrocyte ankyrin-1 complex elucidated by Cryo-EM

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, and sub-tomogram averages of the same complexes from native membrane vesicles. 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 and glycophorin A. 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.

A/Prof. Oliver Clarke

Physiology and Cellular Biophysics 

Anesthesiology & the Irving Institute for Clinical and Translational Research 

Columbia University