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).
Publication Abstract from PubMed
Human 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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ 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. Cryo-EM structure of the human ferritin-transferrin receptor 1 complex. Nat Commun. 2019 Mar 8;10(1):1121. doi: 10.1038/s41467-019-09098-w. PMID:30850661 doi:http://dx.doi.org/10.1038/s41467-019-09098-w
