6XZ6

Structure of the trypanosome brucei factor H receptor bound to domain D5 of bovine factor H

Summary for 6XZ6

• Entry DOI: 10.2210/pdb6xz6/pdb
• Descriptor: GARP domain-containing protein, Complement factor H (3 entities in total)
• Functional Keywords: trypanosome brucei, immunity, complement system, factor h, factor h receptor, immune system
• Biological source: Trypanosoma brucei brucei TREU927; More
• Total number of polymer chains: 4
• Total formula weight: 63572.08

Authors

Macleod, O.J.S.,Carrington, M.,Higgins, M.K. (deposition date: 2020-02-02, release date: 2020-03-25, Last modification date: 2024-11-20)

Primary citation

Macleod, O.J.S.,Bart, J.M.,MacGregor, P.,Peacock, L.,Savill, N.J.,Hester, S.,Ravel, S.,Sunter, J.D.,Trevor, C.,Rust, S.,Vaughan, T.J.,Minter, R.,Mohammed, S.,Gibson, W.,Taylor, M.C.,Higgins, M.K.,Carrington, M.
A receptor for the complement regulator factor H increases transmission of trypanosomes to tsetse flies.
Nat Commun, 11:1326-1326, 2020

PubMed Abstract: Persistent pathogens have evolved to avoid elimination by the mammalian immune system including mechanisms to evade complement. Infections with African trypanosomes can persist for years and cause human and animal disease throughout sub-Saharan Africa. It is not known how trypanosomes limit the action of the alternative complement pathway. Here we identify an African trypanosome receptor for mammalian factor H, a negative regulator of the alternative pathway. Structural studies show how the receptor binds ligand, leaving inhibitory domains of factor H free to inactivate complement C3b deposited on the trypanosome surface. Receptor expression is highest in developmental stages transmitted to the tsetse fly vector and those exposed to blood meals in the tsetse gut. Receptor gene deletion reduced tsetse infection, identifying this receptor as a virulence factor for transmission. This demonstrates how a pathogen evolved a molecular mechanism to increase transmission to an insect vector by exploitation of a mammalian complement regulator.

PubMed: 32165615
DOI: 10.1038/s41467-020-15125-y

Experimental method

X-RAY DIFFRACTION (2.7 Å)