CoChat
Sign Up
Cited by 8Trypanosoma species research and implicationsEnzyme Structure and Functionvaccines and immunoinformatics approaches

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Structural similarities between the metacyclic and bloodstream form variant surface glycoproteins of the African trypanosome

Open access
Chandra, Monica, Đaković, Sara, Foti, Konstantina, Zeelen, Johan P., van Straaten, Monique, Aresta-Branco, Francisco, Tihon, Eliane, Lübbehusen, Nicole, Ruppert, Thomas, Glover, Lucy, Papavasiliou, F. Nina, Stebbins, C. Erec·2023·PLOS Neglected Tropical Diseases
DOI 10.1371/journal.pntd.0011093PMC PMC9956791

Published version of a preprint

Open this paper in CoChat — free accountOpen PDF

Abstract

During infection of mammalian hosts, African trypanosomes thwart immunity using antigenic variation of the dense Variant Surface Glycoprotein (VSG) coat, accessing a large repertoire of several thousand genes and pseudogenes, and switching to antigenically distinct copies. The parasite is transferred to mammalian hosts by the tsetse fly. In the salivary glands of the fly, the pathogen adopts the metacyclic form and expresses a limited repertoire of VSG genes specific to that developmental stage. It has remained unknown whether the metacyclic VSGs possess distinct properties associated with this particular and discrete phase of the parasite life cycle. We present here three novel metacyclic form VSG N-terminal domain crystal structures (mVSG397, mVSG531, and mVSG1954) and show that they mirror closely in architecture, oligomerization, and surface diversity the known classes of bloodstream form VSGs. These data suggest that the mVSGs are unlikely to be a specialized subclass of VSG proteins, and thus could be poor candidates as the major components of prophylactic vaccines against trypanosomiasis.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pntd.0011093

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Show all 2 references

Research works printed but not linked: 58

  1. J Keating, 2015, Human African trypanosomiasis prevention, treatment and control costs: A systematic review, Acta Trop, 150, 4, 10.1016/j.actatropica.2015.06.003 · DOI
  2. A. Ponte-Sucre, 2016, An Overview of Trypanosoma brucei Infections: An Intense Host–Parasite Interaction., Front Microbiol., 7, 10.3389/fmicb.2016.02126 · DOI
  3. KR Matthews, 2015, The within-host dynamics of African trypanosome infections, Philos Trans R Soc Lond B Biol Sci, 370, 10.1098/rstb.2014.0288 · DOI
  4. JD Bangs, 2018, Evolution of Antigenic Variation in African Trypanosomes: Variant Surface Glycoprotein Expression, Structure, and Function., BioEssays, 40, 1800181, 10.1002/bies.201800181 · DOI
  5. PT Manna, 2014, Life and times: synthesis, trafficking, and evolution of VSG, Trends Parasitol, 30, 251, 10.1016/j.pt.2014.03.004 · DOI
  6. P Borst, 1997, Mechanisms of antigenic variation in African trypanosomes, Behring Inst Mitt, 1
  7. D. Horn, 2014, Antigenic variation in African trypanosomes, Mol Biochem Parasitol, 195, 123, 10.1016/j.molbiopara.2014.05.001 · DOI
  8. MR Mugnier, 2016, Masters of Disguise: Antigenic Variation and the VSG Coat in Trypanosoma brucei., PLOS Pathog., 12, e1005784, 10.1371/journal.ppat.1005784 · DOI
  9. F Aresta-Branco, 2019, Mechanistic Similarities between Antigenic Variation and Antibody Diversification during Trypanosoma brucei Infection, Trends Parasitol, 35, 302, 10.1016/j.pt.2019.01.011 · DOI
  10. GA Cross, 2014, Capturing the variant surface glycoprotein repertoire (the VSGnome) of Trypanosoma brucei Lister 427., Mol Biochem Parasitol, 195, 59, 10.1016/j.molbiopara.2014.06.004 · DOI
  11. L Marcello, 2007, Analysis of the VSG gene silent archive in Trypanosoma brucei reveals that mosaic gene expression is prominent in antigenic variation and is favored by archive substructure, Genome Res, 17, 1344, 10.1101/gr.6421207 · DOI
  12. JL Weirather, 2012, Mapping of VSG similarities in Trypanosoma brucei, Mol Biochem Parasitol, 181, 141, 10.1016/j.molbiopara.2011.10.011 · DOI
  13. T Bartossek, 2017, Structural basis for the shielding function of the dynamic trypanosome variant surface glycoprotein coat., Nat Microbiol, 2, 1523, 10.1038/s41564-017-0013-6 · DOI
  14. M Carrington, 1991, Variant specific glycoprotein of Trypanosoma brucei consists of two domains each having an independently conserved pattern of cysteine residues, J Mol Biol, 221, 823, 10.1016/0022-2836(91)80178-W · DOI
  15. D Freymann, 1990, 2.9 A resolution structure of the N-terminal domain of a variant surface glycoprotein from Trypanosoma brucei, J Mol Biol, 216, 141, 10.1016/S0022-2836(05)80066-X · DOI
  16. J Pinger, 2018, African trypanosomes evade immune clearance by O -glycosylation of the VSG surface coat., Nat Microbiol, 3, 932, 10.1038/s41564-018-0187-6 · DOI
  17. J Zeelen, 2021, Structure of trypanosome coat protein VSGsur and function in suramin resistance, Nat Microbiol, 6, 392, 10.1038/s41564-020-00844-1 · DOI
  18. A Chattopadhyay, 2005, Structure of the C-terminal domain from Trypanosoma brucei variant surface glycoprotein MITat1.2, J Biol Chem, 280, 7228, 10.1074/jbc.M410787200 · DOI
  19. NG Jones, 2008, Structure of a glycosylphosphatidylinositol-anchored domain from a trypanosome variant surface glycoprotein, J Biol Chem, 283, 3584, 10.1074/jbc.M706207200 · DOI
  20. K Umaer, 2021, Dynamic, variable oligomerization and the trafficking of variant surface glycoproteins of Trypanosoma brucei, Traffic Cph Den, 22, 274, 10.1111/tra.12806 · DOI
  21. CM Alarcon, 1994, A monocistronic transcript for a trypanosome variant surface glycoprotein, Mol Cell Biol, 14, 5579
  22. SV Graham, 1995, Transcriptional regulation of metacyclic variant surface glycoprotein gene expression during the life cycle of Trypanosoma brucei, Mol Cell Biol, 15, 5945, 10.1128/MCB.15.11.5945 · DOI
  23. S Hutchinson, 2021, The establishment of variant surface glycoprotein monoallelic expression revealed by single-cell RNA-seq of Trypanosoma brucei in the tsetse fly salivary glands., PLOS Pathog., 17, e1009904, 10.1371/journal.ppat.1009904 · DOI
  24. LSM Müller, 2018, Genome organization and DNA accessibility control antigenic variation in trypanosomes, Nature, 563, 121, 10.1038/s41586-018-0619-8 · DOI
  25. P Büscher, 2017, Human African trypanosomiasis, The Lancet, 390, 2397, 10.1016/S0140-6736(17)31510-6 · DOI
  26. KR Matthews, 2005, The developmental cell biology of Trypanosoma brucei, J Cell Sci, 118, 283, 10.1242/jcs.01649 · DOI
  27. G Romero-Meza, 2020, Trypanosoma brucei., Trends Parasitol, 36, 571, 10.1016/j.pt.2019.10.007 · DOI
  28. OA Alfituri, 2020, To the Skin and Beyond: The Immune Response to African Trypanosomes as They Enter and Exit the Vertebrate Host., Front Immunol., 11, 1250, 10.3389/fimmu.2020.01250 · DOI
  29. R Christiano, 2017, The proteome and transcriptome of the infectious metacyclic form of Trypanosoma brucei define quiescent cells primed for mammalian invasion, Mol Microbiol, 106, 74, 10.1111/mmi.13754 · DOI
  30. S Alsford, 2005, Tagging a T. brucei RRNA locus improves stable transfection efficiency and circumvents inducible expression position effects, Mol Biochem Parasitol, 144, 142, 10.1016/j.molbiopara.2005.08.009 · DOI
  31. GA Cross, 1984, Release and purification of Trypanosoma brucei variant surface glycoprotein, J Cell Biochem, 24, 79, 10.1002/jcb.240240107 · DOI
  32. SR Ness, 2004, CRANK: new methods for automated macromolecular crystal structure solution., Struct Lond Engl 1993., 12, 1753
  33. K. Cowtan, 2012, Completion of autobuilt protein models using a database of protein fragments, Acta Crystallogr D Biol Crystallogr, 68, 328, 10.1107/S0907444911039655 · DOI
  34. PD Adams, 2010, PHENIX: a comprehensive Python-based system for macromolecular structure solution, Acta Crystallogr Biol Crystallogr, 66, 213, 10.1107/S0907444909052925 · DOI · Paper page
  35. D Liebschner, 2019, Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix., Acta Crystallogr Sect Struct Biol, 75, 861, 10.1107/S2059798319011471 · DOI · Paper page
  36. P Emsley, 2004, Coot: model-building tools for molecular graphics, Acta Crystallogr D Biol Crystallogr, 60, 2126, 10.1107/S0907444904019158 · DOI · Paper page
  37. RP Joosten, 2014, The PDB_REDO server for macromolecular structure model optimization, IUCrJ, 1, 213, 10.1107/S2052252514009324 · DOI
  38. AJ McCoy, 2007, Phaser crystallographic software, J Appl Crystallogr, 40, 658, 10.1107/S0021889807021206 · DOI · Paper page
  39. TC Terwilliger, 2008, Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard, Acta Crystallogr D Biol Crystallogr, 64, 61, 10.1107/S090744490705024X · DOI · Paper page
  40. GM Sheldrick, 2008, A short history of SHELX, Acta Crystallogr A, 64, 112, 10.1107/S0108767307043930 · DOI
  41. L Potterton, 2018, CCP4i2: the new graphical user interface to the CCP4 program suite, Acta Crystallogr Sect Struct Biol, 74, 68, 10.1107/S2059798317016035 · DOI
  42. G Langer, 2008, Automated macromolecular model building for X-ray crystallography using ARP/wARP version 7., Nat Protoc, 3, 1171, 10.1038/nprot.2008.91 · DOI · Paper page
  43. L Potterton, 2018, CCP 4 i 2: the new graphical user interface to the CCP 4 program suite, Acta Crystallogr Sect Struct Biol, 74, 68, 10.1107/S2059798317016035 · DOI
  44. G. Winter, 2010, xia2: an expert system for macromolecular crystallography data reduction, J Appl Crystallogr, 43, 186, 10.1107/S0021889809045701 · DOI
  45. G Winter, 2022, DIALS as a toolkit, Protein Sci Publ Protein Soc, 31, 232, 10.1002/pro.4224 · DOI
  46. S Wang, 2013, Protein structure alignment beyond spatial proximity, Sci Rep, 3, 1448, 10.1038/srep01448 · DOI
  47. S Wang, 2011, Alignment of distantly related protein structures: algorithm, bound and implications to homology modeling., Bioinforma Oxf Engl, 27, 2537, 10.1093/bioinformatics/btr432 · DOI
  48. G Hovel-Miner, 2015, A Host-Pathogen Interaction Reduced to First Principles: Antigenic Variation in T. brucei., Results Probl Cell Differ, 57, 23, 10.1007/978-3-319-20819-0_2 · DOI
  49. MR Mugnier, 2016, Masters of Disguise: Antigenic Variation and the VSG Coat in Trypanosoma brucei., PLoS Pathog., 12, e1005784, 10.1371/journal.ppat.1005784 · DOI
  50. L Tetley, 1987, Onset of expression of the variant surface glycoproteins of Trypanosoma brucei in the tsetse fly studied using immunoelectron microscopy, J Cell Sci, 87, 363, 10.1242/jcs.87.2.363 · DOI
  51. SV Graham, 1990, Distinct, developmental stage-specific activation mechanisms of trypanosome VSG genes, Parasitology, 101, 361, 10.1017/S0031182000060558 · DOI
  52. JR Helm, 2009, Analysis of expressed sequence tags from the four main developmental stages of Trypanosoma congolense, Mol Biochem Parasitol, 168, 34, 10.1016/j.molbiopara.2009.06.004 · DOI
  53. MR Mugnier, 2015, The in vivo dynamics of antigenic variation in Trypanosoma brucei, Science, 347, 1470, 10.1126/science.aaa4502 · DOI
  54. S McNicholas, 2011, Presenting your structures: the CCP4mg molecular-graphics software, Acta Crystallogr D Biol Crystallogr, 67, 386, 10.1107/S0907444911007281 · DOI
  55. RA Laskowski, 2018, PDBsum: Structural summaries of PDB entries, Protein Sci, 27, 129, 10.1002/pro.3289 · DOI
  56. D Eisenberg, 1984, Analysis of membrane and surface protein sequences with the hydrophobic moment plot, J Mol Biol, 179, 125, 10.1016/0022-2836(84)90309-7 · DOI
  57. EF Pettersen, 2004, UCSF Chimera—a visualization system for exploratory research and analysis, J Comput Chem, 25, 1605, 10.1002/jcc.20084 · DOI
  58. P Emsley, 2010, Features and development of Coot, Acta Crystallogr D Biol Crystallogr, 66, 486, 10.1107/S0907444910007493 · DOI · Paper page

Metadata

Authors
Chandra, M., Đaković, S., Foti, K., Zeelen, J. P., van Straaten, M., Aresta-Branco, F., Tihon, E., Lübbehusen, N., Ruppert, T., Glover, L., Papavasiliou, F. N., & Stebbins, C. E.
Affiliations
  • German Cancer Research Center (DE)
  • Institut Pasteur (FR)
  • Heidelberg University (DE)
Corresponding author
  • Papavasiliou, F. Nina
  • Stebbins, C. Erec
ORCID
Venue
PLOS Neglected Tropical Diseases
Publisher
Public Library of Science (PLoS)
Published
2023-02-13
Volume
17
Issue
2
Pages
e0011093
ISSN
  • 1935-2727 (ISSN-L)
  • 1935-2735
DOI
10.1371/journal.pntd.0011093
PMC
PMC9956791
OpenAlex
W4320482007
Cited by
8
References
2
Citations by year
2026: 2 · 2024: 4 · 2023: 2
FWCI
1.60
Type
journal article
Language
en
Update notices
new_version (2023-02-24)
Open access
Licence
Locations
  • PLoS neglected tropical diseases (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • DORA PSI (Paul Scherrer Institute) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Agence Nationale de la Recherche (ANR-17-CE12-0012 VSGREG)
  • Deutsches Krebsforschungszentrum
Topics
  • Health Sciences › Medicine › Epidemiology › Trypanosoma species research and implications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Keywords
African trypanosomes, Trypanosoma brucei, variant surface glycoprotein, metacyclic forms, bloodstream forms, antigenic variation, N-terminal domain, oligomerization, parasite life cycle
MeSH terms
Animals, Mammals, Membrane Glycoproteins, Trypanosoma, Trypanosoma brucei brucei, Trypanosomiasis, African, Tsetse Flies, Variant Surface Glycoproteins, Trypanosoma

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review