6Z8H

Crystal structure of Variant Surface Glycoprotein VSG13

6Z8H の概要

• エントリーDOI: 10.2210/pdb6z8h/pdb
• 分子名称: Variant surface glycoprotein MITat 1.13, alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: variant surface glycoprotein, immune recognition, immune evasion, trypanosomiasis, membrane protein
• 由来する生物種: Trypanosoma brucei
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 109208.31

構造登録者

Stebbins, C.E.,Hempelmann, A.,Van Straaten, M.,Zeelen, J. (登録日: 2020-06-02, 公開日: 2021-03-17, 最終更新日: 2024-10-23)

主引用文献

Zeelen, J.,van Straaten, M.,Verdi, J.,Hempelmann, A.,Hashemi, H.,Perez, K.,Jeffrey, P.D.,Halg, S.,Wiedemar, N.,Maser, P.,Papavasiliou, F.N.,Stebbins, C.E.
Structure of trypanosome coat protein VSGsur and function in suramin resistance.
Nat Microbiol, 6:392-400, 2021

PubMed 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.

PubMed: 33462435
DOI: 10.1038/s41564-020-00844-1

実験手法

X-RAY DIFFRACTION (1.38 Å)