6gsr
Single Particle Cryo-EM map of human Transferrin receptor 1 - H-Ferritin complex at 5.5 Angstrom resolution.Single Particle Cryo-EM map of human Transferrin receptor 1 - H-Ferritin complex at 5.5 Angstrom resolution.
Structural highlights
Function[FRIH_HUMAN] Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role in delivery of iron to cells. Mediates iron uptake in capsule cells of the developing kidney (By similarity). [TFR1_HUMAN] Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes. Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system (By similarity). A second ligand, the heditary hemochromatosis protein HFE, competes for binding with transferrin for an overlapping C-terminal binding site.[1] Publication Abstract from PubMedHuman transferrin receptor 1 (CD71) guarantees iron supply by endocytosis upon binding of iron-loaded transferrin and ferritin. Arenaviruses and the malaria parasite exploit CD71 for cell invasion and epitopes on CD71 for interaction with transferrin and pathogenic hosts were identified. Here, we provide the molecular basis of the CD71 ectodomain-human ferritin interaction by determining the 3.9 A resolution single-particle cryo-electron microscopy structure of their complex and by validating our structural findings in a cellular context. The contact surfaces between the heavy-chain ferritin and CD71 largely overlap with arenaviruses and Plasmodium vivax binding regions in the apical part of the receptor ectodomain. Our data account for transferrin-independent binding of ferritin to CD71 and suggest that select pathogens may have adapted to enter cells by mimicking the ferritin access gate. Cryo-EM structure of the human ferritin-transferrin receptor 1 complex.,Montemiglio LC, Testi C, Ceci P, Falvo E, Pitea M, Savino C, Arcovito A, Peruzzi G, Baiocco P, Mancia F, Boffi A, des Georges A, Vallone B Nat Commun. 2019 Mar 8;10(1):1121. doi: 10.1038/s41467-019-09098-w. PMID:30850661[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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