| Title: |
Structure of the trypanosome transferrin receptor reveals mechanisms of ligand recognition and immune evasion. |
| Authors: |
Trevor, Camilla E; Gonzalez-Munoz, Andrea L; Macleod, Olivia JS; Woodcock, Peter G; Rust, Steven; Vaughan, Tristan J; Garman, Elspeth F; Minter, Ralph; Carrington, Mark; Higgins, Matthew K |
| Publisher Information: |
Nature Research https://doi.org/10.1038/s41564-019-0589-0 Nature Microbiology 2021-01-07T00:30:58Z 2021-01-07T00:30:58Z 2019-12 |
| Document Type: |
Electronic Resource |
| Abstract: |
To maintain prolonged infection of mammals, African trypanosomes have evolved remarkable surface coats and a system of antigenic variation1. Within these coats are receptors for macromolecular nutrients such as transferrin2,3. 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 receptors4, which has been proposed to allow binding to transferrin from different mammalian hosts5,6. 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. |
| Index Terms: |
Antigenic Variation; Genetic Variation; Host-Parasite Interactions; Humans; Immune Evasion; Ligands; Models, Molecular; Protein Binding; Protein Structure, Tertiary; Protozoan Proteins; Receptors, Transferrin; Transferrin; Trypanosoma brucei brucei; Trypanosomiasis, African; Article |
| URL: |
https://www.repository.cam.ac.uk/handle/1810/315813 |
| Availability: |
Open access content. Open access content; All rights reserved |
| Note: |
application/pdf; English; English |
| Other Numbers: |
HS1 oai:www.repository.cam.ac.uk:1810/315813; 10.17863/CAM.62922; 1489045835 |
| Contributing Source: |
UNIV OF CAMBRIDGE; From OAIster®, provided by the OCLC Cooperative. |
| Accession Number: |
edsoai.on1489045835 |
| Database: |
OAIster |