6soz | pdb_00006soz
Glycosylated Trypanosoma brucei transferrin receptor in complex with human transferrin
Structural highlights
Disease[TRFE_HUMAN] Defects in TF are the cause of atransferrinemia (ATRAF) [MIM:209300]. Atransferrinemia is rare autosomal recessive disorder characterized by iron overload and hypochromic anemia.[1] [2] Function[TRFE_HUMAN] Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation. Publication Abstract from PubMedTo maintain prolonged infection of mammals, African trypanosomes have evolved remarkable surface coats and a system of antigenic variation(1). Within these coats are receptors for macromolecular nutrients such as transferrin(2,3). These must be accessible to their ligands but must not confer susceptibility to immunoglobulin-mediated attack. Trypanosomes have a wide host range and their receptors must also bind ligands from diverse species. To understand how these requirements are achieved, in the context of transferrin uptake, we determined the structure of a Trypanosoma brucei transferrin receptor in complex with human transferrin, showing how this heterodimeric receptor presents a large asymmetric ligand-binding platform. The trypanosome genome contains a family of around 14 transferrin receptors(4), which has been proposed to allow binding to transferrin from different mammalian hosts(5,6). However, we find that a single receptor can bind transferrin from a broad range of mammals, indicating that receptor variation is unlikely to be necessary for promiscuity of host infection. In contrast, polymorphic sites and N-linked glycans are preferentially found in exposed positions on the receptor surface, not contacting transferrin, suggesting that transferrin receptor diversification is driven by a need for antigenic variation in the receptor to prolong survival in a host. Structure of the trypanosome transferrin receptor reveals mechanisms of ligand recognition and immune evasion.,Trevor CE, Gonzalez-Munoz AL, Macleod OJS, Woodcock PG, Rust S, Vaughan TJ, Garman EF, Minter R, Carrington M, Higgins MK Nat Microbiol. 2019 Oct 21. pii: 10.1038/s41564-019-0589-0. doi:, 10.1038/s41564-019-0589-0. PMID:31636418[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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