蛋白酶体
MHC I级
肽
主要组织相容性复合体
泛素
蛋白质降解
生物
细胞生物学
细胞内
MHC II级
蛋白质水解
抗原呈递
生物化学
计算生物学
免疫系统
遗传学
T细胞
酶
基因
作者
Jennifer L. Mamrosh,David J. Sherman,Joseph R. Cohen,James A. Johnston,Marisa K. Joubert,J. Li,J. Russell Lipford,Brett Lomenick,Annie Moradian,Siddharth Prabhu,Michael J. Sweredoski,Bryan Vander Lugt,Rati Verma,Raymond J. Deshaies
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2023-06-23
卷期号:9 (25)
被引量:3
标识
DOI:10.1126/sciadv.ade7890
摘要
Peptides from degradation of intracellular proteins are continuously displayed by major histocompatibility complex (MHC) class I. To better understand origins of these peptides, we performed a comprehensive census of the class I peptide repertoire in the presence and absence of ubiquitin-proteasome system (UPS) activity upon developing optimized methodology to enrich for and quantify these peptides. Whereas most class I peptides are dependent on the UPS for their generation, a surprising 30%, enriched in peptides of mitochondrial origin, appears independent of the UPS. A further ~10% of peptides were found to be dependent on the proteasome but independent of ubiquitination for their generation. Notably, clinically achievable partial inhibition of the proteasome resulted in display of atypical peptides. Our results suggest that generation of MHC class I•peptide complexes is more complex than previously recognized, with UPS-dependent and UPS-independent components; paradoxically, alternative protein degradation pathways also generate class I peptides when canonical pathways are impaired.
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