ジャーナル: Nat Commun / 年: 2019 タイトル: Cryo-EM structure of the human ferritin-transferrin receptor 1 complex. 著者: Linda Celeste Montemiglio / Claudia Testi / Pierpaolo Ceci / Elisabetta Falvo / Martina Pitea / Carmelinda Savino / Alessandro Arcovito / Giovanna Peruzzi / Paola Baiocco / Filippo Mancia / ...著者: Linda Celeste Montemiglio / Claudia Testi / Pierpaolo Ceci / Elisabetta Falvo / Martina Pitea / Carmelinda Savino / Alessandro Arcovito / Giovanna Peruzzi / Paola Baiocco / Filippo Mancia / Alberto Boffi / Amédée des Georges / Beatrice Vallone / 要旨: 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 ...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.
Aa: Ferritin heavy chain Ab: Transferrin receptor protein 1 Ac: Ferritin heavy chain Ad: Ferritin heavy chain Ae: Ferritin heavy chain Af: Ferritin heavy chain Ag: Ferritin heavy chain Ah: Ferritin heavy chain Ai: Ferritin heavy chain Aj: Ferritin heavy chain Ak: Ferritin heavy chain Al: Ferritin heavy chain Am: Ferritin heavy chain An: Ferritin heavy chain Ao: Ferritin heavy chain Ap: Ferritin heavy chain Aq: Transferrin receptor protein 1 Ar: Ferritin heavy chain As: Ferritin heavy chain At: Ferritin heavy chain Au: Ferritin heavy chain Av: Ferritin heavy chain Aw: Ferritin heavy chain Ax: Ferritin heavy chain Ay: Ferritin heavy chain Az: Ferritin heavy chain