The major diagnostic VSG LiTat 1.3 of the human parasite Trypanosoma brucei gambiense is a trimer in solution.

Authors

Niki Danel, Rob Geens, Israel Mares-Mejía, Wim Versées, Jan Van Den Abbeele, Yann G J Sterckx

Published in

PLoS pathogens. Volume 22. Issue 8. Pages e1014530. Aug 10, 2026. Epub Aug 10, 2026.

Abstract

Human African trypanosomiasis (HAT) remains a significant health burden in sub-Saharan Africa, with serological diagnosis relying heavily on parasite variant surface glycoproteins (VSGs). Experimentally validated structural studies of VSGs from Trypanosoma brucei gambiense (the main HAT causative agent) are currently lacking despite their diagnostic importance. In this study, we present a thorough characterization of LiTat 1.3, a key VSG in the diagnosis of T. b. gambiense infections, through an integrative structural biology approach encompassing AlphaFold-based structure prediction, analytical gel filtration (AGF), size exclusion chromatography with multi-angle light scattering (SEC-MALS), and small-angle X-ray scattering (SAXS). While sequence-based analyses had previously proposed LiTat 1.3 as a homotrimeric B2 class VSG, experimental evidence was yet to be presented. Here, we demonstrate that LiTat 1.3 displays a stable, concentration-independent homotrimeric architecture in solution, which is distinct from other trimeric T. brucei brucei VSGs described to date. Furthermore, the SAXS data demonstrate that the C-terminal domains of trimeric VSGs exhibit the same degree of flexibility as observed in dimeric VSGs. Hence, the biophysical characterization of LiTat 1.3 VSG adds to the growing body of knowledge that certain VSG classes occur as homotrimers instead of homodimers. Together, these results not only expand our knowledge of VSG structure and flexibility but also provide the first detailed structural insight into a major diagnostic VSG of T. b. gambiense, which holds potential for understanding antibody recognition and guiding the development of improved serological tests.

PMID:
42574507
Bibliographic data and abstract were imported from PubMed on 11 Aug 2026.

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