4zrq
From Proteopedia
E88 deletion mutant of CD320 in complex with TC2
Structural highlights
Disease[TCO2_HUMAN] Defects in TCN2 are the cause of transcobalamin II deficiency (TCN2 deficiency) [MIM:275350]. This results in various forms of anemia. [CD320_HUMAN] Methylmalonic aciduria due to transcobalamin receptor defect. The disease is caused by mutations affecting the gene represented in this entry. Function[TCO2_HUMAN] Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells. [CD320_HUMAN] Germinal center-B (GC-B) cells differentiate into memory B-cells and plasma cells (PC) through interaction with T-cells and follicular dendritic cells (FDC). CD320 augments the proliferation of PC precursors generated by IL-10. Receptor for the cellular uptake of transcobalamin bound cobalamin.[1] [2] Publication Abstract from PubMedCellular uptake of vitamin B12 (cobalamin) requires capture of transcobalamin (TC) from the plasma by CD320, a ubiquitous cell surface receptor of the LDLR family. Here we present the crystal structure of human holo-TC in complex with the extracellular domain of CD320, visualizing the structural basis of the TC-CD320 interaction. The observed interaction chemistry can rationalize the high affinity of CD320 for TC and lack of haptocorrin binding. The in vitro affinity and complex stability of TC-CD320 were quantitated using a solid-phase binding assay and thermostability analysis. Stable complexes with TC were also observed for the disease-causing CD320DeltaE88 mutant and for the isolated LDLR-A2 domain. We also determined the structure of the TC-CD320DeltaE88 complex, which revealed only minor changes compared with the wild-type complex. Finally, we demonstrate significantly reduced in vitro affinity of TC for CD320 at low pH, recapitulating the proposed ligand release during the endocytic pathway. Structural basis of transcobalamin recognition by human CD320 receptor.,Alam A, Woo JS, Schmitz J, Prinz B, Root K, Chen F, Bloch JS, Zenobi R, Locher KP Nat Commun. 2016 Jul 14;7:12100. doi: 10.1038/ncomms12100. PMID:27411955[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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