Current research on the human band 3 glycoprotein, the red cell chloride/bicarbonate anion exchanger (AE1), is highlighted and placed within a structural context.
The determination of the crystal structure of the membrane domain of human band 3, the founding member of the solute carrier 4 (SLC4) family of bicarbonate transporters, is a major breakthrough toward understanding the mechanism of action of this membrane transport protein, its interaction with partner proteins, and how mutations linked to disease affect its ability to fold and function.
Band 3 contains 14 transmembrane segments arranged in a 7+7 transmembrane inverted repeat topology common to all members of the SLC4 family and the unrelated SLC26 anion transporter family. A functional feature of this fold is the presence of a core and a gate domain: the core domain contains two short transmembrane helices (TM3 and 10) that face each other in the middle of the membrane with the positive N-terminal helix dipoles creating the anion-binding site, whereas the gate domain forms the dimer interface. During transport, the movement of these two domains relative to each other provides the intracellular and extracellular compartments with alternating access to the central anion-binding site.
aHospital for Sick Children Research Institute, Toronto, Ontario, Canada
bSchool of Biochemistry, University of Bristol, Biomedical Sciences Building
cBristol Institute of Transfusion Science, NHS Blood and Transplant, Filton, Bristol, UK
dDepartment of Medical Biophysics, University of Toronto
eDepartment of Biochemistry, University of Toronto, Toronto, Ontario, Canada
Correspondence to Reinhart A.F. Reithmeier, University of Toronto, Toronto, Ontario M5S 1A8, Canada. E-mail: email@example.com