ArticleNature microbiology2021
Structure of trypanosome coat protein VSGsur and function in suramin resistance.
Article in Nature microbiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 32 citations in OpenAlex.
- Suramin Interactions Across Biological Systems: From Molecular Targets to Therapeutic Implications.Biomolecules · 2026Review
- Evasive mechanisms of human VSG and PfEMP1 antigens with link to Vaccine scenario: a review.Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2025Review
- Drug resistance in animal trypanosomiases: Epidemiology, mechanisms and control strategies.International journal for parasitology. Drugs and drug resistance · 2024Review
- Structural insights into drug transport by an aquaglyceroporin.Nature communications · 2024Article
- A structural classification of the variant surface glycoproteins of the African trypanosome.PLoS neglected tropical diseases · 2023Article
- Tackling Sleeping Sickness: Current and Promising Therapeutics and Treatment Strategies.International journal of molecular sciences · 2023Review
- The role of invariant surface glycoprotein 75 in xenobiotic acquisition by African trypanosomes.Microbial cell (Graz, Austria) · 2023Article
- Structural similarities between the metacyclic and bloodstream form variant surface glycoproteins of the African trypanosome.PLoS neglected tropical diseases · 2023Article
- Systematic Review and Meta-Analysis on Human African Trypanocide Resistance.Pathogens (Basel, Switzerland) · 2022Review
- Effects of Suramin on Polycystic Kidney Disease in a Mouse Model of Polycystin-1 Deficiency.International journal of molecular sciences · 2022Article
- Learning from Yeast about Mitochondrial Carriers.Microorganisms · 2021Review
- The Glycosylphosphatidylinositol Anchor: A Linchpin for Cell Surface Versatility of Trypanosomatids.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
Suramin has been a primary early-stage treatment for African trypanosomiasis for nearly 100 yr. Recent studies revealed that trypanosome strains that express the variant surface glycoprotein (VSG) VSGsur possess heightened resistance to suramin. Here, we show that VSGsur binds tightly to suramin but other VSGs do not. By solving high-resolution crystal structures of VSGsur and VSG13, we also demonstrate that these VSGs define a structurally divergent subgroup of the coat proteins. The co-crystal structure of VSGsur with suramin reveals that the chemically symmetric drug binds within a large cavity in the VSG homodimer asymmetrically, primarily through contacts of its central benzene rings. Structure-based, loss-of-contact mutations in VSGsur significantly decrease the affinity to suramin and lead to a loss of the resistance phenotype. Altogether, these data show that the resistance phenotype is dependent on the binding of suramin to VSGsur, establishing that the VSG proteins can possess functionality beyond their role in antigenic variation.
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Registered trials
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