7ty7

Cryo-EM structure of human Anion Exchanger 1 bound to Bicarbonate

spinqualitylabelsall models 7ty7, resolution 3.37Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7ty7 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.37Å Ligands: BCT, CLR, NAG, PC1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. 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. 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), a member of the solute carrier (SLC) family, is the primary bicarbonate transporter in erythrocytes, regulating pH levels and CO(2) transport between lungs and tissues. Previous studies characterized its role in erythrocyte structure and provided insight into transport regulation. However, key questions remain regarding substrate binding and transport, mechanisms of drug inhibition and modulation by membrane components. Here we present seven cryo-EM structures in apo, bicarbonate-bound and inhibitor-bound states. These, combined with uptake and computational studies, reveal important molecular features of substrate recognition and transport, and illuminate sterol binding sites, to elucidate distinct inhibitory mechanisms of research chemicals and prescription drugs. We further probe the substrate binding site via structure-based ligand screening, identifying an AE1 inhibitor. Together, our findings provide insight into mechanisms of solute carrier transport and inhibition. Substrate binding and inhibition of the anion exchanger 1 transporter.,Capper MJ, Yang S, Stone AC, Vatansever S, Zilberg G, Mathiharan YK, Habib R, Hutchinson K, Zhao Y, Schlessinger A, Mezei M, Osman R, Zhang B, Wacker D Nat Struct Mol Biol. 2023 Oct;30(10):1495-1504. doi: 10.1038/s41594-023-01085-6. , Epub 2023 Sep 7. PMID:37679563 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Anion exchange protein 3D structures

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