Redox regulation of peptide receptivity of major histocompatibility complex class I molecules by ERp57 and tapasin
Redox regulation of peptide receptivity of major histocompatibility complex class I molecules by ERp57 and tapasin
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DOI：
10.1038/ni1483
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发表时间：
2007-08-01
影响因子：
30.5
通讯作者：
Dick, Tobias P.
中科院分区：
文献类型：
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作者：
Kienast, Alexandra;Preuss, Marc;Dick, Tobias P.
氧化还原酶ERp57在主要组织相容性复合物（MHC）I类肽负载复合物中的功能仍然难以捉摸。在这里，我们表明，在没有tapasin，α（2）二硫键的MHC I类肽结合沟迅速减少。需要通过tapasin共价螯合ERp57以保护α（2）二硫键不被还原，从而将结合沟维持在肽接受状态。MHC I类tapasin依赖性的等位基因变异反映了它们对α（2）二硫键还原的易感性。在没有螯合作用的情况下，ERp57直接作用于α（2）二硫键。我们的工作为免疫系统如何定制内质网中的“质量控制”以适应抗原呈递的需要提供了见解。
The function of the oxidoreductase ERp57 in the major histocompatibility complex (MHC) class I peptide-loading complex has remained elusive. Here we show that in the absence of tapasin, the alpha(2) disulfide bond in the MHC class I peptide-binding groove was rapidly reduced. Covalent sequestration of ERp57 by tapasin was needed to protect the alpha(2) disulfide bond against reduction and thus to maintain the binding groove in a peptide-receptive state. Allelic variations in MHC class I tapasin dependency reflected their susceptibility to reduction of the alpha(2) disulfide bond. In the absence of sequestration, ERp57 acted directly on the alpha(2) disulfide bond. Our work provides insight into how the immune system customizes 'quality control' in the endoplasmic reticulum to fit the needs of antigen presentation.