Band 3 macrocomplex and proposed gas exchange metabolon.

(A) Schematic diagram of the band 3 macrocomplex showing probable interactions of the proteins that form the band 3 macrocomplex. Tetramers of band 3 are attached to the spectrin cytoskeleton through ankyrin. The acidic N-terminal region of the cytoplasmic domain of band 3 binds deoxy-hemoglobin, hemichromes, glyceraldehyde-3-phosphate dehydrogenase (G3PD), and aldolase.4 The short C-terminal cytoplasmic tail of band 3 binds CAII.3 The GPA dimer is close to the membrane domain of band 3. Protein 4.2 binds ankyrin, band 3, and CD47 (in humans), providing one link between the Rh complex and the band 3 complex.27 CD47 and LW are closely associated with the Rh tetramers9 and may be involved in adhesive interactions with the capillary surface.22,23 The Rh tetramer associates directly with band 3. GPB associates with the Rh tetramers,9 and GPA and GPB may form heterotetramers, providing another link between the Rh complex and the band 3 complex. (B) Proposed gas exchange metabolon in the RBC membrane. The model suggests that CO₂ passes from the capillary endothelial cell to the RBC through the Rh proteins. CAII converts CO₂and H₂O to HCO$3−$ and a proton, and HCO$3−$ passes out of the RBC through band 3 in exchange for a chloride ion. The removal of HCO$3−$ leaves a proton that promotes local acidification in the vicinity of band 3 and the release of oxygen from oxy-hemoglobin by the Bohr effect. O₂ may then leave the RBC through the Rh gas channel and pass into the endothelial cells. The channeling of substrate through this metabolon reduces substrate loss by diffusion from the system. In the pulmonary microcapillaries, the system would be reversed. Water movements involved in the hydration/dehydration of CO₂ may be mediated by AQP1,55 though AQP1 is not directly associated with the band 3 macrocomplex.