Cutting Edge: HLA-DM-Mediated Peptide Exchange Functions Normally on MHC Class II-Peptide Complexes That Have Been Weakened by Elimination of a Conserved Hydrogen Bond
Cutting Edge: HLA-DM-Mediated Peptide Exchange Functions Normally on MHC Class II-Peptide Complexes That Have Been Weakened by Elimination of a Conserved Hydrogen Bond
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DOI：
10.4049/jimmunol.0902878
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发表时间：
2010-02-01
影响因子：
4.4
通讯作者：
Gorski, Jack
中科院分区：
文献类型：
--
作者：
Ferrante, Andrea;Gorski, Jack
HLA-DM（DM）促进与HLA-DR（DR）结合的肽交换的机制尚不清楚。我们已经表明，肽与DR 1的相互作用可以被认为是一个折叠过程，证明了协同性。然而，在DM-介导的配体交换中，预结合肽的释放是不合作的，这可能是关键相互作用的破坏的函数。β-链His（81）和肽骨架之间在-1位置的氢键（H-键）是这种靶点的候选者。在这项研究中，我们分析的交换结合到DR 1的肽。这种氢键的形成受到损害的突变体。我们观察到DM仍然正常工作。然而，正如合作模型所预期的那样，该H-键有助于复合物的整体能量学，并且其破坏影响交换配体与结合槽折叠成稳定复合物的能力。免疫学杂志，2010，184：1153-1158。
The mechanism by which HLA-DM (DM) promotes exchange of peptides bound to HLA-DR (DR) is still unclear. We have shown that peptide interaction with DR1 can be considered a folding process as evidenced by cooperativity. However, in DM-mediated ligand exchange, prebound peptide release is noncooperative, which could be a function of the breaking of a critical interaction. The hydrogen bond (H-bond) between beta-chain His(81) and the peptide backbone at the -1 position is a candidate for such a target. In this study, we analyze the exchange of peptides bound to a DR1. mutant in which formation of this H-bond is impaired. We observe that DM still functions normally. However, as expected of a cooperative model, this H-bond contributes to the overall energetics of the complex and its disruption impacts the ability of the exchange ligand to fold with the binding groove into a stable complex. The Journal of Immunology, 2010, 184: 1153-1158.