ERAP1-ERAP2 dimers trim MHC I-bound precursor peptides; implications for understanding peptide editing.
ERAP1-ERAP2 dimers trim MHC I-bound precursor peptides; implications for understanding peptide editing.
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DOI：
10.1038/srep28902
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发表时间：
2016-08-12
影响因子：
4.6
通讯作者：
Bouvier M
中科院分区：
文献类型：
--
作者：
Chen H;Li L;Weimershaus M;Evnouchidou I;van Endert P;Bouvier M
内质网氨肽酶1（ERAP 1）和ERAP 2对MHC I类抗原前体肽的加工是抗原呈递细胞生物学中的重要事件。迄今为止，ERAP酶修剪前体肽的分子背景，以及ERAP如何塑造肽库，仍然是悬而未决的问题。使用ERAP 1和ERAP 2异二聚体（ERAP 1/2），和N-末端延伸的模型和天然肽在其自由和HLA-B*0801结合的形式，我们的特点ERAP的作用模式。我们提供的证据表明，ERAP 1/2可以修剪MHC I结合的前体肽，以其正确的和最终的长度，虽然比相应的自由前体更慢。ERAP 1/2对MHC I结合前体的修饰增加了MHC I/肽复合物的构象稳定性。根据这些数据，我们提出了ERAP 1/2作为肽编辑器的分子机制模型。总体而言，我们的研究提供了新的发现ERAP介导的处理途径的MHC I类抗原的一个重要问题。
The processing of MHC class I antigenic precursor peptides by the endoplasmic reticulum aminopeptidase 1 (ERAP1) and ERAP2 is an important event in the cell biology of antigen presentation. To date, the molecular context by which the ERAP enzymes trim precursor peptides, and how ERAPs shape peptide repertoires, remain open questions. Using ERAP1 and ERAP2 heterodimers (ERAP1/2), and N-terminally extended model and natural peptides in their free and HLA-B*0801-bound forms, we characterized the mode of action of ERAPs. We provide evidence that ERAP1/2 can trim MHC I-bound precursor peptides to their correct and final lengths, albeit more slowly than the corresponding free precursors. Trimming of MHC I-bound precursors by ERAP1/2 increases the conformational stability of MHC I/peptide complexes. From the data, we propose a molecular mechanistic model of ERAP1/2 as peptide editors. Overall, our study provides new findings on a significant issue of the ERAP-mediated processing pathway of MHC class I antigens.