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Cited by 5Trypanosoma species research and implicationsProtein Structure and DynamicsGlycosylation and Glycoproteins Research

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Beyond the VSG layer: Exploring the role of intrinsic disorder in the invariant surface glycoproteins of African trypanosomes

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Sülzen, Hagen, Volkov, Alexander N., Geens, Rob, Zahedifard, Farnaz, Stijlemans, Benoit, Zoltner, Martin, Magez, Stefan, Sterckx, Yann G.-J., Zoll, Sebastian·2024·PLOS Pathogens
DOI 10.1371/journal.ppat.1012186PMC PMC11065263

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Abstract

In the bloodstream of mammalian hosts, African trypanosomes face the challenge of protecting their invariant surface receptors from immune detection. This crucial role is fulfilled by a dense, glycosylated protein layer composed of variant surface glycoproteins (VSGs), which undergo antigenic variation and provide a physical barrier that shields the underlying invariant surface glycoproteins (ISGs). The protective shield’s limited permeability comes at the cost of restricted access to the extracellular host environment, raising questions regarding the specific function of the ISG repertoire. In this study, we employ an integrative structural biology approach to show that intrinsically disordered membrane-proximal regions are a common feature of members of the ISG super-family, conferring the ability to switch between compact and elongated conformers. While the folded, membrane-distal ectodomain is buried within the VSG layer for compact conformers, their elongated counterparts would enable the extension beyond it. This dynamic behavior enables ISGs to maintain a low immunogenic footprint while still allowing them to engage with the host environment when necessary. Our findings add further evidence to a dynamic molecular organization of trypanosome surface antigens wherein intrinsic disorder underpins the characteristics of a highly flexible ISG proteome to circumvent the constraints imposed by the VSG coat.

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Metadata

Authors
Sülzen, H., Volkov, A. N., Geens, R., Zahedifard, F., Stijlemans, B., Zoltner, M., Magez, S., Sterckx, Y. G.-J., & Zoll, S.
Affiliations
  • Czech Academy of Sciences (CZ)
  • Vrije Universiteit Brussel (BE)
  • University of Antwerp (BE)
  • Charles University (CZ)
Corresponding author
  • Sterckx, Yann G.-J.
  • Zoll, Sebastian
ORCID
Venue
PLOS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2024-04-22
Volume
20
Issue
4
Pages
e1012186
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.1012186
PMC
PMC11065263
OpenAlex
W4394995725
Cited by
5
References
4
Citations by year
2026: 1 · 2025: 2 · 2024: 2
FWCI
1.53
Type
journal article
Language
en
Update notices
new_version (2024-05-02)
Open access
Licence
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • VUBIR (Vrije Universiteit Brussel) (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Grantová Agentura České Republiky (22-21612S)
  • Grantová Agentura, Univerzita Karlova (383821/2600)
  • DOCPRO4- NIEUWZAP (code 40043)
  • Bijzonder Onderzoeksfond
  • Strategic Research Program (SRP3 and SRP47, VUB)
  • OPVVV (0000759)
Topics
  • Health Sciences › Medicine › Epidemiology › Trypanosoma species research and implications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
Keywords
African trypanosomes, variant surface glycoprotein, intrinsic disorder, antigenic variation, conformational switching, membrane-proximal region, immune evasion, Trypanosoma brucei
MeSH terms
Animals, Humans, Membrane Glycoproteins, Trypanosomiasis, African, Variant Surface Glycoproteins, Trypanosoma, Protozoan Proteins

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