6ELU

Structure of Serum Resistance Associated protein from T. b. rhodesiense

Summary for 6ELU

• Entry DOI: 10.2210/pdb6elu/pdb
• Descriptor: Serum resistance associated; VSG protein, G10_3 heavy chain, G10_3 Light chain, ... (4 entities in total)
• Functional Keywords: tryanosome, innate immune evasion, sleeping sickness, apolipoprotein li, sra, trypanolytic factor., antitoxin
• Biological source: Trypanosoma brucei rhodesiense; More
• Total number of polymer chains: 12
• Total formula weight: 292148.07

Authors

Zoll, S.,Higgins, M.K. (deposition date: 2017-09-29, release date: 2018-01-24, Last modification date: 2024-10-23)

Primary citation

Zoll, S.,Lane-Serff, H.,Mehmood, S.,Schneider, J.,Robinson, C.V.,Carrington, M.,Higgins, M.K.
The structure of serum resistance-associated protein and its implications for human African trypanosomiasis.
Nat Microbiol, 3:295-301, 2018

PubMed Abstract: Only two trypanosome subspecies are able to cause human African trypanosomiasis. To establish an infection in human blood, they must overcome the innate immune system by resisting the toxic effects of trypanolytic factor 1 and trypanolytic factor 2 (refs. ). These lipoprotein complexes contain an active, pore-forming component, apolipoprotein L1 (ApoL1), that causes trypanosome cell death . One of the two human-infective subspecies, Trypanosoma brucei rhodesiense, differs from non-infective trypanosomes solely by the presence of the serum resistance-associated protein, which binds directly to ApoL1 and blocks its pore-forming capacity. Since this interaction is the single critical event that renders T. b. rhodesiense human- infective, detailed structural information that allows identification of binding determinants is crucial to understand immune escape by the parasite. Here, we present the structure of serum resistance-associated protein and reveal the adaptations that occurred as it diverged from other trypanosome surface molecules to neutralize ApoL1. We also present our mapping of residues important for ApoL1 binding, giving molecular insight into this interaction at the heart of human sleeping sickness.

PubMed: 29358741
DOI: 10.1038/s41564-017-0085-3

Experimental method

X-RAY DIFFRACTION (2.3 Å)