Cryo-EM structures of the human band 3 transporter indicate a transport mechanism involving the coupled movement of chloride and bicarbonate ions

• Published in: PLoS biology Vol. 22; no. 8; p. e3002719
• Main Authors: Su, Chih-Chia, Zhang, Zhemin, Lyu, Meinan, Cui, Meng, Yu, Edward W
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21-08-2024; Public Library of Science (PLoS)
• Subjects: Anion Exchange Protein 1, Erythrocyte - chemistry; Anion Exchange Protein 1, Erythrocyte - metabolism; Bicarbonates; Bicarbonates - metabolism; Biology and Life Sciences; Carrier proteins; Cell Membrane - metabolism; Chlorides; Chlorides - metabolism; Cryoelectron microscopy; Cryoelectron Microscopy - methods; Dichloropropane; Humans; Ion Transport; Ions; Methods; Models, Molecular; Physical Sciences; Physiological aspects; Protein Conformation; Protein Multimerization; Research and Analysis Methods; United States
• ISSN: 1544-9173; 1545-7885; 1545-7885
• DOI: 10.1371/journal.pbio.3002719

The band 3 transporter is a critical integral membrane protein of the red blood cell (RBC), as it is responsible for catalyzing the exchange of bicarbonate and chloride anions across the plasma membrane. To elucidate the structural mechanism of the band 3 transporter, detergent solubilized human ghost membrane reconstituted in nanodiscs was applied to a cryo-EM holey carbon grid to define its composition. With this approach, we identified and determined structural information of the human band 3 transporter. Here, we present 5 different cryo-EM structures of the transmembrane domain of dimeric band 3, either alone or bound with chloride or bicarbonate. Interestingly, we observed that human band 3 can form both symmetric and asymmetric dimers with a different combination of outward-facing (OF) and inward-facing (IF) states. These structures also allow us to obtain the first model of a human band 3 molecule at the IF conformation. Based on the structural data of these dimers, we propose a model of ion transport that is in favor of the elevator-type mechanism.