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 Å 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, Linda Celeste; Testi, Claudia; Ceci, Pierpaolo; Falvo, Elisabetta; Pitea, Martina; Savino, Carmelinda; Arcovito, Alessandro; Peruzzi, Giovanna; Baiocco, Paola; Mancia, Filippo; Boffi, Alberto; des Georges, Amédée; Vallone, Beatrice. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 10:1(2019), p. 1121. [10.1038/s41467-019-09098-w]

Cryo-EM structure of the human ferritin–transferrin receptor 1 complex

Montemiglio, Linda Celeste;Testi, Claudia;Ceci, Pierpaolo;Falvo, Elisabetta;Pitea, Martina;Savino, Carmelinda;Arcovito, Alessandro;Peruzzi, Giovanna;Baiocco, Paola;Mancia, Filippo;Boffi, Alberto;Vallone, Beatrice
2019

Abstract

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 Å 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.
2019
chemistry (all); biochemistry, genetics and molecular biology (all); physics and astronomy (all)
01 Pubblicazione su rivista::01a Articolo in rivista
Cryo-EM structure of the human ferritin–transferrin receptor 1 complex / Montemiglio, Linda Celeste; Testi, Claudia; Ceci, Pierpaolo; Falvo, Elisabetta; Pitea, Martina; Savino, Carmelinda; Arcovito, Alessandro; Peruzzi, Giovanna; Baiocco, Paola; Mancia, Filippo; Boffi, Alberto; des Georges, Amédée; Vallone, Beatrice. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 10:1(2019), p. 1121. [10.1038/s41467-019-09098-w]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1254997
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