期刊
NATURE MICROBIOLOGY
卷 3, 期 8, 页码 932-938出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41564-018-0187-6
关键词
-
类别
资金
- NIH/NIGMS grant [P41 GM103403]
- NIH-ORIP HEI grant [S10 RR029205]
- DOE Office of Science [DE-AC02-06CH11357]
- German Cancer Research Center (DKFZ, Heidelberg)
- Rockefeller University
- NIH/NIAID [AI085973]
- Wellcome Trust Senior Investigator Award [101842]
- Wellcome Trust [097045]
- NATIONAL CENTER FOR RESEARCH RESOURCES [S10RR029205] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI085973] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P41GM103403] Funding Source: NIH RePORTER
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-angstrom-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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据