The functional architecture of band 3, the anion transport protein of the red cell membrane.
Band 3 is an abundant, intrinsic, transmembrane peptide of about 95 000 daltons that mediates anion exchanges across the red blood cell membrane. It is present in the membrane as a dimer with each monomer arranged so that it crosses the bilayer at least five times. Based on proteolytic dissection and the use of covalent probes to "mark" specific sites, it is proposed that the crossing strands form an assembly of alpha-helices, with hydrophobic residues exposed so they are closely associated with the fatty acid side chains of the phospholipids and with hydrophilic residues internalized to form an aqueous core through which transport occurs. Anions cannot freely diffuse through the transport pathway, but are constrained by a "gating" mechanism that requires an electroneutral one-for-one exchange. The process involves the binding of the anions to specific transport sites followed by a local conformational change, such that the sites (with the bound anion) alternate between states that are topologically in and out, with kinetics consistent with a "ping-pong" mechanism. Large organic anions can bind to the transport sites resulting in competitive inhibition. Those such as 4,4'-diisothiocyano-2,2'-stilbene sulfonic acid that can react covalently have been used to mark the transport site in the primary structure of band 3. Sequence data will ultimately allow a much more detailed assessment of the functional architecture of band 3.
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000345:Affinity Labels / Q000494:pharmacology; D001457:Anion Exchange Protein 1, Erythrocyte / Q000302:isolation & purification / Q000378:metabolism*; D000838:Anions; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008051:Lipid Bilayers; D008563:Membrane Lipids / Q000097:blood; D010446:Peptide Fragments / Q000032:analysis; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology
D000345:Affinity Labels; D001457:Anion Exchange Protein 1, Erythrocyte; D000838:Anions; D008051:Lipid Bilayers; D008563:Membrane Lipids; D010446:Peptide Fragments; D013654:Taurine; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; C010861:NAP taurine; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid