Thanks to the revolutionary technique of cryogenic electron microscopy, a group of researchers from the Sapienza “A. Rossi Fanelli” Department of Biochemistry and the IIT@Sapienza Lab observed how the mechanism through which cells incorporate iron is the same used by viruses to infect them.
The results, published on Nature Communication, pave the way to the development of precision drugs against viruses and tumours. This was a teamwork supported by the Prometeus-Rise Consortium.
A research team, directed by Beatrice Vallone and Alberto Boffi, from the Sapienza “A. Rossi Fanelli” Department of Biochemistry and the IIT@Sapienza Lab observed for the first time the structure of the complex formed by the ferritin protein and its cellular receptor (CD17). The analysis structure of the ferritin-receptor complex has revealed an important and previously unknown biological mechanism: the process through which iron enters into cells. The results of the study, published on Nature Communication, not only enlarge the panorama of basic scientific knowledge, but will also have important practical consequences.
The researchers discovered that the malaria plasmodium and viruses of the arenavirus and parvovirus families gain access to cells and infect them using the same area utilized by ferritin. The knowledge of this mechanism will allow researchers to devise a strategy to deceive viruses by producing small molecules that will block their access to the part of the receptor that allows them to bind and enter cells.
The results were obtained by using cryogenic electron microscopy, a technique that allows determination of the three-dimensional structures of macromolecules with atomic details and that earned Jacques Dubochet, Joachim Frank and Richard Henderson the Nobel Prize in Chemistry in 2017. These last-generation electron microscopes are available at Columbia University, the Advanced Science Research Center at the City University of New York and at the European Synchrotron Research Facility, where Sapienza researchers Linda Celeste Montemiglio and Claudia Testi collaborated on the research project.
The study also has another important implication for medicine: it will allow the creation of new nano-vectors for the diagnosis and cure of cancer. The Sapienza research team (ValloneLab), in collaboration with the Cnr Institute of Molecular Biology and Pathology, have been exploiting the ferritin-receptor as a “molecular key” to selectively drive anti-tumour drugs since several years.
“Now, the we fully understand the structure of the complex,” explains Project Coordinator Beatrice Vallone, “we will be able to develop more specific, selective and efficient therapies.”
Cryo-EM structure of the human Ferritin-Transferrin Receptor 1 complex – Montemiglio, L.C., 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. – Nature Communication 2019. DOI: 10.1038/s41467-019-09098-w