4ky9

From Proteopedia

(Difference between revisions)

Revision as of 14:51, 5 January 2015

Structural and Functional Analysis of a Putative Substrate Access Tunnel in the Cytosolic Domain of Human Anion Exchanger 1

Structural highlights

4ky9 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	SLC4A1, AE1, DI, EPB3 (HUMAN)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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

Anion exchanger 1 (AE1; Band 3; SLC4A1) is the founding member of the solute carrier 4 (SLC4) family of bicarbonate transporters that includes chloride/bicarbonate AEs and Na(+)-bicarbonate co-transporters (NBCs). These membrane proteins consist of an amino-terminal cytosolic domain involved in protein interactions and a carboxyl-terminal membrane domain that carries out the transport function. Mutation of a conserved arginine residue (R298S) in the cytosolic domain of NBCe1 (SLC4A4) is linked to proximal renal tubular acidosis and results in impaired transport function, suggesting that the cytosolic domain plays a role in substrate permeation. Introduction of single and double mutations at the equivalent arginine (Arg(283)) and at an interacting glutamate (Glu(85)) in the cytosolic domain of human AE1 (cdAE1) had no effect on the cell surface expression or the transport activity of AE1 expressed in HEK-293 cells. In addition, the membrane domain of AE1 (mdAE1) efficiently mediated anion transport. A 2.1-A resolution crystal structure of cdDelta54AE1 (residues 55-356 of cdAE1) lacking the amino-terminal and carboxyl-terminal disordered regions, produced at physiological pH, revealed an extensive hydrogen-bonded network involving Arg(283) and Glu(85). Mutations at these residues affected the pH-dependent conformational changes and stability of cdDelta54AE1. As these structural alterations did not impair functional expression of AE1, the cytosolic and membrane domains operate independently. A substrate access tunnel within the cytosolic domain is not present in AE1 and therefore is not an essential feature of the SLC4 family of bicarbonate transporters.

A substrate access tunnel in the cytosolic domain is not an essential feature of the solute carrier 4 (SLC4) family of bicarbonate transporters.,Shnitsar V, Li J, Li X, Calmettes C, Basu A, Casey JR, Moraes TF, Reithmeier RA J Biol Chem. 2013 Nov 22;288(47):33848-60. doi: 10.1074/jbc.M113.511865. Epub, 2013 Oct 11. PMID:24121512^[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
↑ Shnitsar V, Li J, Li X, Calmettes C, Basu A, Casey JR, Moraes TF, Reithmeier RA. A substrate access tunnel in the cytosolic domain is not an essential feature of the solute carrier 4 (SLC4) family of bicarbonate transporters. J Biol Chem. 2013 Nov 22;288(47):33848-60. doi: 10.1074/jbc.M113.511865. Epub, 2013 Oct 11. PMID:24121512 doi:http://dx.doi.org/10.1074/jbc.M113.511865

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4ky9"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4ky9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KY9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KY9 FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SLC4A1, AE1, DI, EPB3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SLC4A1, AE1, DI, EPB3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ky9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ky9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ky9 RCSB], [http://www.ebi.ac.uk/pdbsum/4ky9 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ky9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ky9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ky9 RCSB], [http://www.ebi.ac.uk/pdbsum/4ky9 PDBsum]</span></td></tr>
-<table>
+</table>
 == Disease ==
 [[http://www.uniprot.org/uniprot/B3AT_HUMAN B3AT_HUMAN]] Defects in SLC4A1 are the cause of elliptocytosis type 4 (EL4) [MIM:[http://omim.org/entry/109270 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.<ref>PMID:1722314</ref> <ref>PMID:1538405</ref>   Defects in SLC4A1 are the cause of spherocytosis type 4 (SPH4) [MIM:[http://omim.org/entry/612653 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.<ref>PMID:8547122</ref> <ref>PMID:1378323</ref> <ref>PMID:7530501</ref> <ref>PMID:8943874</ref> <ref>PMID:8640229</ref> <ref>PMID:9207478</ref> <ref>PMID:9012689</ref> <ref>PMID:9233560</ref> <ref>PMID:9973643</ref> <ref>PMID:10580570</ref> <ref>PMID:10942416</ref> <ref>PMID:10745622</ref> <ref>PMID:11380459</ref> <ref>PMID:15813913</ref> <ref>PMID:16227998</ref>   Defects in SLC4A1 are the cause of renal tubular acidosis, distal, autosomal dominant (AD-dRTA) [MIM:[http://omim.org/entry/179800 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:[http://omim.org/entry/611590 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:[http://omim.org/entry/611590 611590]]. A disease characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis.
@@ Line 23: / Line 23: @@
 </StructureSection>
 [[Category: Human]]
-[[Category: Calmettes, C.]]
+[[Category: Calmettes, C]]
-[[Category: Moraes, T F.]]
+[[Category: Moraes, T F]]
-[[Category: Reithmeier, R A.F.]]
+[[Category: Reithmeier, R A.F]]
-[[Category: Shnitsar, V.]]
+[[Category: Shnitsar, V]]
 [[Category: Cytosolic domain]]
 [[Category: Membrane protein]]

4ky9

From Proteopedia

Revision as of 14:51, 5 January 2015

Structural and Functional Analysis of a Putative Substrate Access Tunnel in the Cytosolic Domain of Human Anion Exchanger 1

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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