The Diego blood group system-an update

Poole, Joyce

doi:10.21307/immunohematology-2019-635

Cited by 10 publications

(2 citation statements)

References 38 publications

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“…We further reveal the complete extracellular surface of the transporter (Fig 1) including all extracellular loop regions and glycosylation sites of both protomers. We were able to map the position and architecture of all Diego blood group antigens located on AE1 (Extended Data Figure 1D), revealing the detailed molecular architecture of the epitopes targeted in various hemolytic diseases 1,2,17 .…”

Section: Resultsmentioning

confidence: 99%

“…AE1 is a key transporter in red blood cells (RBC) where it shuttles CO 2 between lungs and other tissues via bicarbonate transport and contributes to the structural integrity of RBCs through interactions with the cytoskeleton. AE1’s extracellular surface binds antibodies of the Diego antigen system, a blood group of 21 antigens that can cause potentially fatal hemolytic disease of the newborn 1 : Antibodies produced by the mother can bind epitopes on AE1, thereby attacking RBCs of the fetus or the newborn 2 . Other mutations can disrupt AE1 structure and/or transport resulting in red blood cell deformities and kidney diseases such as renal acidosis 3,4 .…”

Section: Introductionmentioning

confidence: 99%

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Substrate Binding and Inhibition of the Anion Exchanger 1 Transporter

Capper

Yang

Stone

et al. 2022

Preprint

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Anion Exchanger 1 (AE1, SLC4A1) is the primary bicarbonate (HCO3-) transporter expressed in erythrocyte membranes where it mediates transport of CO2 between lungs and other tissues via import/export of bicarbonate. It is also a key regulator of erythrocyte structure and antigenic recognition. Previous biochemical studies, and a low-resolution crystal structure of the transmembrane domain have provided initial insight into AE1 structure and function. However, key questions remain regarding substrate binding and transport as well as the mechanism of inhibition. The orientation of the intracellular domain as well as the localization of lipid and sterol binding sites also remain enigmatic. We herein present seven novel high resolution cryo-EM structures of the full length human transporter in the apo, bicarbonate-bound, and several inhibitor-bound states combined with uptake- and computational studies. To our knowledge, these studies represent the first full length human, and substrate bound, SLC4 transporter structure. Our results reveal important molecular details about substrate binding and transport, as well as the diverse mechanisms of AE1 inhibition by both research chemicals and prescription drugs. We also provide novel insights into the full-length transporter architecture, identify the conformational space of the Diego blood antigen system and elucidate multiple lipid and sterol binding sites.

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Section: Resultsmentioning

confidence: 99%