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

Authors

Linda Celeste Montemiglio, Sapienza University of Rome
Claudia Testi, Sapienza University of Rome
Pierpaolo Ceci, Institute of Molecular Biology and Pathology, Rome
Elisabetta Falvo, Institute of Molecular Biology and Pathology, Rome
Martina Pitea, Sapienza University of Rome
Carmelinda Savino, Institute of Molecular Biology and Pathology, Rome
Alessandro Arcovito, Università Cattolica del Sacro Cuore
Giovanna Peruzzi, Istituto Italiano di Tecnologia
Paola Baiocco, Istituto Italiano di Tecnologia
Filippo Mancia, Columbia University
Alberto Boffi, Sapienza University of Rome
Amédée des Georges, CUNY City CollegeFollow
Beatrice Vallone, Sapienza University of Rome

Document Type

Article

Publication Date

3-8-2019

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.

Comments

This article was originally published in Nature Communications, available at DOI: 10.1038/s41467-019-09098-w.

This article is licensed under a Creative Commons Attribution 4.0 International License.