| Structural highlights
Disease
B3AT_HUMAN Defects in SLC4A1 are the cause of elliptocytosis type 4 (EL4) [MIM:109270. EL4 is a Rhesus-unlinked form of hereditary elliptocytosis, a genetically heterogeneous, autosomal dominant hematologic disorder. It is characterized by variable hemolytic anemia and elliptical or oval red cell shape.[1] [2] Defects in SLC4A1 are the cause of spherocytosis type 4 (SPH4) [MIM:612653; also known as hereditary spherocytosis type 4 (HS4). Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal.[3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] Defects in SLC4A1 are the cause of renal tubular acidosis, distal, autosomal dominant (AD-dRTA) [MIM:179800. A disease characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. Defects in SLC4A1 are the cause of renal tubular acidosis, distal, with hemolytic anemia (dRTA-HA) [MIM:611590. A disease characterized by the association of hemolytic anemia with distal renal tubular acidosis, the reduced ability to acidify urine resulting in variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. Defects in SLC4A1 are the cause of renal tubular acidosis, distal, with normal red cell morphology (dRTA-NRC) [MIM:611590. A disease characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis.
Function
B3AT_HUMAN Band 3 is the major integral glycoprotein of the erythrocyte membrane. Band 3 has two functional domains. Its integral domain mediates a 1:1 exchange of inorganic anions across the membrane, whereas its cytoplasmic domain provides binding sites for cytoskeletal proteins, glycolytic enzymes, and hemoglobin.
Publication Abstract from PubMed
A protein-protein association regulated by phosphorylation of tyrosine is examined by NMR structural studies and biochemical studies. Binding of glyceraldehyde-3-phosphate dehydrogenase (G3PDH) and aldolase to the N-terminus of human erythrocyte anion transporter, band 3, inhibits enzyme activity. This inhibition is reversed upon phosphorylation of band 3 Y8, as shown by kinetic studies on purified components, as well as in vivo studies. Thus, tyrosine phosphorylation mediates against the intermolecular protein-protein association, in contrast to the positive control involving SH2 and PTB domains where phosphorylation is required for binding. To elucidate the basis of recognition and negative control by tyrosine phosphorylation, the structure of a synthetic peptide, B3P, corresponding to the first 15 residues of band 3 (MEELQDDYEDMMEEN-NH2), bound to G3PDH has been determined using the exchange-transferred nuclear Overhauser effect. The G3PDH-bound B3P structure was found to be very similar to the structure recognized by aldolase. A hydrophobic triad forms from side chains within a loop structure of residues 4 through 9 in both bound species. Another structural feature stabilizing the loop, in the case of the B3P-G3PDH complex, is a hydrogen bond between the side chains of Y8 and D10 associated with a beta-turn of residues 8-11. Based on the structure of this phosphorylation sensitive interaction (PSI) loop, it is suggested that tyrosine phosphorylation disrupts protein-protein association, in part, by intramolecular electrostatic destabilization. The inhibition by B3P is competitive with respect to the coenzyme NAD+ and noncompetitive with the substrate analog arsenate. Specific binding of B3P to G3PDH is demonstrated by reversion of the NMR spectral properties of bound B3P to those of the free peptide upon addition of coenzyme and substrate analog. The stoichiometry of binding for the B3P-G3PDH complex was determined from Sephadex G-50 displacement experiments to be 4:1. Collectively, these results are consistent with B3P binding the active site of G3PDH.
Insights into tyrosine phosphorylation control of protein-protein association from the NMR structure of a band 3 peptide inhibitor bound to glyceraldehyde-3-phosphate dehydrogenase.,Eisenmesser EZ, Post CB Biochemistry. 1998 Jan 20;37(3):867-77. PMID:9454576[18]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jarolim P, Palek J, Amato D, Hassan K, Sapak P, Nurse GT, Rubin HL, Zhai S, Sahr KE, Liu SC. Deletion in erythrocyte band 3 gene in malaria-resistant Southeast Asian ovalocytosis. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11022-6. PMID:1722314
- ↑ Schofield AE, Tanner MJ, Pinder JC, Clough B, Bayley PM, Nash GB, Dluzewski AR, Reardon DM, Cox TM, Wilson RJ, et al.. Basis of unique red cell membrane properties in hereditary ovalocytosis. J Mol Biol. 1992 Feb 20;223(4):949-58. PMID:1538405
- ↑ Maillet P, Vallier A, Reinhart WH, Wyss EJ, Ott P, Texier P, Baklouti F, Tanner MJ, Delaunay J, Alloisio N. Band 3 Chur: a variant associated with band 3-deficient hereditary spherocytosis and substitution in a highly conserved position of transmembrane segment 11. Br J Haematol. 1995 Dec;91(4):804-10. PMID:8547122
- ↑ Jarolim P, Palek J, Rubin HL, Prchal JT, Korsgren C, Cohen CM. Band 3 Tuscaloosa: Pro327----Arg327 substitution in the cytoplasmic domain of erythrocyte band 3 protein associated with spherocytic hemolytic anemia and partial deficiency of protein 4.2. Blood. 1992 Jul 15;80(2):523-9. PMID:1378323
- ↑ Jarolim P, Rubin HL, Brabec V, Chrobak L, Zolotarev AS, Alper SL, Brugnara C, Wichterle H, Palek J. Mutations of conserved arginines in the membrane domain of erythroid band 3 lead to a decrease in membrane-associated band 3 and to the phenotype of hereditary spherocytosis. Blood. 1995 Feb 1;85(3):634-40. PMID:7530501
- ↑ Jarolim P, Murray JL, Rubin HL, Taylor WM, Prchal JT, Ballas SK, Snyder LM, Chrobak L, Melrose WD, Brabec V, Palek J. Characterization of 13 novel band 3 gene defects in hereditary spherocytosis with band 3 deficiency. Blood. 1996 Dec 1;88(11):4366-74. PMID:8943874
- ↑ Eber SW, Gonzalez JM, Lux ML, Scarpa AL, Tse WT, Dornwell M, Herbers J, Kugler W, Ozcan R, Pekrun A, Gallagher PG, Schroter W, Forget BG, Lux SE. Ankyrin-1 mutations are a major cause of dominant and recessive hereditary spherocytosis. Nat Genet. 1996 Jun;13(2):214-8. PMID:8640229 doi:10.1038/ng0696-214
- ↑ Alloisio N, Texier P, Vallier A, Ribeiro ML, Morle L, Bozon M, Bursaux E, Maillet P, Goncalves P, Tanner MJ, Tamagnini G, Delaunay J. Modulation of clinical expression and band 3 deficiency in hereditary spherocytosis. Blood. 1997 Jul 1;90(1):414-20. PMID:9207478
- ↑ Miraglia del Giudice E, Vallier A, Maillet P, Perrotta S, Cutillo S, Iolascon A, Tanner MJ, Delaunay J, Alloisio N. Novel band 3 variants (bands 3 Foggia, Napoli I and Napoli II) associated with hereditary spherocytosis and band 3 deficiency: status of the D38A polymorphism within the EPB3 locus. Br J Haematol. 1997 Jan;96(1):70-6. PMID:9012689
- ↑ Dhermy D, Galand C, Bournier O, Boulanger L, Cynober T, Schismanoff PO, Bursaux E, Tchernia G, Boivin P, Garbarz M. Heterogenous band 3 deficiency in hereditary spherocytosis related to different band 3 gene defects. Br J Haematol. 1997 Jul;98(1):32-40. PMID:9233560
- ↑ Iwase S, Ideguchi H, Takao M, Horiguchi-Yamada J, Iwasaki M, Takahara S, Sekikawa T, Mochizuki S, Yamada H. Band 3 Tokyo: Thr837-->Ala837 substitution in erythrocyte band 3 protein associated with spherocytic hemolysis. Acta Haematol. 1998;100(4):200-3. PMID:9973643 doi:40904
- ↑ Lima PR, Sales TS, Costa FF, Saad ST. Arginine 490 is a hot spot for mutation in the band 3 gene in hereditary spherocytosis. Eur J Haematol. 1999 Nov;63(5):360-1. PMID:10580570
- ↑ Ribeiro ML, Alloisio N, Almeida H, Gomes C, Texier P, Lemos C, Mimoso G, Morle L, Bey-Cabet F, Rudigoz RC, Delaunay J, Tamagnini G. Severe hereditary spherocytosis and distal renal tubular acidosis associated with the total absence of band 3. Blood. 2000 Aug 15;96(4):1602-4. PMID:10942416
- ↑ Yawata Y, Kanzaki A, Yawata A, Doerfler W, Ozcan R, Eber SW. Characteristic features of the genotype and phenotype of hereditary spherocytosis in the Japanese population. Int J Hematol. 2000 Feb;71(2):118-35. PMID:10745622
- ↑ Bracher NA, Lyons CA, Wessels G, Mansvelt E, Coetzer TL. Band 3 Cape Town (E90K) causes severe hereditary spherocytosis in combination with band 3 Prague III. Br J Haematol. 2001 Jun;113(3):689-93. PMID:11380459
- ↑ Lima PR, Baratti MO, Chiattone ML, Costa FF, Saad ST. Band 3Tambau: a de novo mutation in the AE1 gene associated with hereditary spherocytosis. Implications for anion exchange and insertion into the red blood cell membrane. Eur J Haematol. 2005 May;74(5):396-401. PMID:15813913 doi:10.1111/j.1600-0609.2004.00405.x
- ↑ Bruce LJ, Robinson HC, Guizouarn H, Borgese F, Harrison P, King MJ, Goede JS, Coles SE, Gore DM, Lutz HU, Ficarella R, Layton DM, Iolascon A, Ellory JC, Stewart GW. Monovalent cation leaks in human red cells caused by single amino-acid substitutions in the transport domain of the band 3 chloride-bicarbonate exchanger, AE1. Nat Genet. 2005 Nov;37(11):1258-63. Epub 2005 Oct 9. PMID:16227998 doi:10.1038/ng1656
- ↑ Eisenmesser EZ, Post CB. Insights into tyrosine phosphorylation control of protein-protein association from the NMR structure of a band 3 peptide inhibitor bound to glyceraldehyde-3-phosphate dehydrogenase. Biochemistry. 1998 Jan 20;37(3):867-77. PMID:9454576 doi:https://dx.doi.org/10.1021/bi971445b
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