Structural analysis of the transferrin receptor multifaceted ligand(s) interface

Abstract

The transferrin receptor 1 (TfR1) is one of the key regulators of iron homeostasis for most higher organisms. It mediates cellular iron import through a constitutive clathrin-dependent endocytosis mechanism and by recruiting iron- regulator proteins as transferrin, Hereditary Hemochromatosis factor (HFE) and serum ferritin in response to cellular demand. The receptor is also opportunistically exploited by several viruses and the malaria parasite as a preferential door for cell invasion. In this review, we analyze the structural information available for TfR1 and all its functional complexes to figure out how structural signals in a single receptor can guide the recognition of multiple ligands and how the conservation of key residues in TfR1 might have a role in iron uptake and cell infection.

Keywords: Ferritin; Iron import regulation; Multiple ligand binding; Transferrin and HFE; Transferrin receptor; Virus and Plasmodium vivax.