title: Slow transitions between two conformational states of band 3 (AE1) modulate divalent anion transport and DBDS binding to a second site on band 3 which is activated by lowering the pH (pK approximately 5.0).
abstract: Evidence is emerging which indicates that the anion transport activity of band 3 may be regulated. I review the molecular basis for regulation of the anion transport function of band 3 in terms of evidence showing that divalent anion transport involves a slow "hysteretic" transition between two functional states, mediated by interactions between subunits within band 3 oligomers. In addition, I briefly describe recent work from my laboratory where we have discovered a novel manifestation of slow conformational changes in band 3. This involves 4,4'-dibenzamido-2,2'-stilbenedisulfonate (DBDS) binding to a second, proton-activated site distinct from the primary stilbenedisulfonate site. This site is exposed on the outer aspect of band 3 when the pH is lowered (pK approximately 5.0). This is the same pK as the protonation site on band 3 involved in divalent anion-proton co-transport (APCT) [J. Gen. Physiol. 79 (1982) 87]. Significantly, we have found that DBDS binding to this proton-activated site has unusually slow kinetics, and increasing DBDS concentration causes a decrease in the apparent pseudo-first-order rate constant. These results suggest that a slow conformational pre-equilibrium is the rate limiting step in DBDS binding to the proton-activated site on band 3 observed at low pH. Our results support an allosteric two-state model for regulation of divalent anion transport by band 3 oligomers involving a slow conformational transition and interactions between subunits [Biochemistry 31 (1992) 7301].
authors.affiliation: The Veterans Administration Medical Center and Departments of Internal Medicine and Biochemistry and Molecular Biology, University of Nebraska Medical Center, 984510 Nebraska Medical Center, Omaha, NE 68198-4510, USA. jsalhan@attglobal.net
authors.forename: James M
authors.initials: JM
authors.lastname: Salhany
mesh_terms: D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D000494:Allosteric Regulation; D000495:Allosteric Site; D001457:Anion Exchange Protein 1, Erythrocyte / Q000037:antagonists & inhibitors / Q000737:chemistry*; D000838:Anions / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D011487:Protein Conformation
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D000838:Anions; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; C036010:4,4'-dibenzamido-2,2'-stilbenedisulfonic acid