Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53201, USA.
J Immunol. 2010 Feb 1;184(3):1153-8. doi: 10.4049/jimmunol.0902878. Epub 2009 Dec 28.
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.
HLA-DM（DM）促进与 HLA-DR（DR）结合的肽交换的机制仍不清楚。我们已经表明，与 DR1 的肽相互作用可以被认为是一个折叠过程，这是由协同作用证明的。然而，在 DM 介导的配体交换中，预结合的肽释放是非协同的，这可能是关键相互作用被打破的功能。β链 His（81）与 -1 位肽主链之间的氢键（H 键）是这种靶标的候选物。在这项研究中，我们分析了与 DR1 突变体结合的肽的交换，该突变体中形成这种 H 键的能力受损。我们观察到 DM 仍然正常发挥作用。然而，正如协同模型所预期的那样，这种氢键有助于复合物的整体能量，其破坏会影响交换配体与结合槽折叠成稳定复合物的能力。
