Format

Send to

Choose Destination
Nat Commun. 2019 Mar 8;10(1):1121. doi: 10.1038/s41467-019-09098-w.

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

Author information

1
Department of Biochemical Sciences "Alessandro Rossi Fanelli", Sapienza University of Rome, P.le A. Moro 5, 00185, Rome, Italy.
2
Institute of Molecular Biology and Pathology, National Research Council, P.le A. Moro 5, 00185, Rome, Italy.
3
Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Scienze Biochimiche "A. Rossi Fanelli", Sapienza Università di Roma, P.le A. Moro 5, 00185, Rome, Italy.
4
Center for Life Nano Science @ Sapienza, Istituto Italiano di Tecnologia, V.le Regina Elena 291, 00161, Rome, Italy.
5
Istituto di Biochimica e Biochimica Clinica, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168, Rome, Italy.
6
Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Largo F. Vito 1, 00168, Rome, Italy.
7
Department of Physiology and Cellular Biophysics, Russ Berrie Pavilion, Columbia University Medical Center, 1150 St Nicholas Ave, New York, NY, 10032, USA.
8
Advanced Science Research Center at The Graduate Center of the City University of New York, 85 Saint Nicholas Terrace, New York, NY, 10031, USA. amedee.desgeorges@asrc.cuny.edu.
9
Department of Chemistry and Biochemistry, City College of New York, New York, NY, 10031, USA. amedee.desgeorges@asrc.cuny.edu.
10
Programs in Biochemistry and Chemistry, The Graduate Center of the City University of New York, New York, NY, 10016, USA. amedee.desgeorges@asrc.cuny.edu.
11
Department of Biochemical Sciences "Alessandro Rossi Fanelli", Sapienza University of Rome, P.le A. Moro 5, 00185, Rome, Italy. beatrice.vallone@uniroma1.it.
12
Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Scienze Biochimiche "A. Rossi Fanelli", Sapienza Università di Roma, P.le A. Moro 5, 00185, Rome, Italy. beatrice.vallone@uniroma1.it.

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.

PMID:
30850661
PMCID:
PMC6408514
DOI:
10.1038/s41467-019-09098-w
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center