Hydrophobicity as a driver of MHC class I antigen processing
Hydrophobicity as a driver of MHC class I antigen processing
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DOI：
10.1038/emboj.2011.62
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发表时间：
2011-04-20
期刊：
影响因子：
11.4
通讯作者：
Eisenlohr, Laurence C.
中科院分区：
文献类型：
--
作者：
Huang, Lan;Kuhls, Matthew C.;Eisenlohr, Laurence C.
驱动新生蛋白质转化为主要组织相容性复合体（MHC）I类限制性肽的力量仍然未知。我们探索了明显的疏水性作为这样的驱动程序的基本属性。通过信号序列消融将膜糖蛋白重新定位到胞质溶胶导致新生蛋白的快速加工，这不是因为错误折叠的管腔结构域，而是因为未嵌入的跨膜（TM）结构域，其作为剂量依赖性降解基序。在内质网相关降解（ERAD）的自然过程中，TM结构域的错位同样加速了肽的产生，但在显着延长的处理，包括nonnascent物种的背景下。这些见解细胞内蛋白水解途径和它们的选择性贡献MHC I类限制性肽供应，可能会指出新的方法，在合理的疫苗设计。The EMBO Journal（2011）30，1634-1644. doi：10.1038/djj.2011.62;在线发表2011年3月4日主题分类：蛋白质;免疫学
The forces that drive conversion of nascent protein to major histocompatibility complex (MHC) class I-restricted peptides remain unknown. We explored the fundamental property of overt hydrophobicity as such a driver. Relocation of a membrane glycoprotein to the cytosol via signal sequence ablation resulted in rapid processing of nascent protein not because of the misfolded luminal domain but because of the unembedded transmembrane (TM) domain, which serves as a dose-dependent degradation motif. Dislocation of the TM domain during the natural process of endoplasmic reticulum-associated degradation (ERAD) similarly accelerated peptide production, but in the context of markedly prolonged processing that included nonnascent species. These insights into intracellular proteolytic pathways and their selective contributions to MHC class I-restricted peptide supply, may point to new approaches in rational vaccine design. The EMBO Journal (2011) 30, 1634-1644. doi:10.1038/emboj.2011.62; Published online 4 March 2011 Subject Categories: proteins; immunology