Structural highlights
Publication Abstract from PubMedThe 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-A-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. African trypanosomes evade immune clearance by O-glycosylation of the VSG surface coat.,Pinger J, Nesic D, Ali L, Aresta-Branco F, Lilic M, Chowdhury S, Kim HS, Verdi J, Raper J, Ferguson MAJ, Papavasiliou FN, Stebbins CE Nat Microbiol. 2018 Jul 9. pii: 10.1038/s41564-018-0187-6. doi:, 10.1038/s41564-018-0187-6. PMID:29988048[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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