6ELC

Crystal Structure of O-linked Glycosylated VSG3

Summary for 6ELC

• Entry DOI: 10.2210/pdb6elc/pdb
• Descriptor: Variant surface glycoprotein, alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: trypanosome, vsg, sleeping sickness, antigen, immune system
• Biological source: Trypanosoma brucei brucei
• Total number of polymer chains: 1
• Total formula weight: 54863.23

Authors

Stebbins, C.E. (deposition date: 2017-09-28, release date: 2018-07-11, Last modification date: 2024-10-16)

Primary citation

Pinger, J.,Nesic, D.,Ali, L.,Aresta-Branco, F.,Lilic, M.,Chowdhury, S.,Kim, H.S.,Verdi, J.,Raper, J.,Ferguson, M.A.J.,Papavasiliou, F.N.,Stebbins, C.E.
African trypanosomes evade immune clearance by O-glycosylation of the VSG surface coat.
Nat Microbiol, 3:932-938, 2018

PubMed Abstract: The African trypanosome Trypanosoma brucei spp. is a paradigm for antigenic variation, the orchestrated alteration of cell surface molecules to evade host immunity. The parasite elicits robust antibody-mediated immune responses to its variant surface glycoprotein (VSG) coat, but evades immune clearance by repeatedly accessing a large genetic VSG repertoire and 'switching' to antigenically distinct VSGs. This persistent immune evasion has been ascribed exclusively to amino-acid variance on the VSG surface presented by a conserved underlying protein architecture. We establish here that this model does not account for the scope of VSG structural and biochemical diversity. The 1.4-Å-resolution crystal structure of the variant VSG3 manifests divergence in the tertiary fold and oligomeric state. The structure also reveals an O-linked carbohydrate on the top surface of VSG3. Mass spectrometric analysis indicates that this O-glycosylation site is heterogeneously occupied in VSG3 by zero to three hexose residues and is also present in other VSGs. We demonstrate that this O-glycosylation increases parasite virulence by impairing the generation of protective immunity. These data alter the paradigm of antigenic variation by the African trypanosome, expanding VSG variability beyond amino-acid sequence to include surface post-translational modifications with immunomodulatory impact.

PubMed: 29988048
DOI: 10.1038/s41564-018-0187-6

Experimental method

X-RAY DIFFRACTION (1.41 Å)