Davies Matthew N, Lamikanra Abigail, Sansom Clare E, Flower Darren R, Moss David S, Travers Paul J
Edward Jenner Institute, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Headley Way, Headington, Oxford OX3 9DU, UK.
Mol Immunol. 2008 Feb;45(4):1063-70. doi: 10.1016/j.molimm.2007.07.033. Epub 2007 Sep 17.
Human leukocyte antigen (HLA)-DM is a critical participant in antigen presentation that catalyzes the dissociation of the Class II-associated Invariant chain-derived Peptide (CLIP) from the major histocompatibility complex (MHC) Class II molecules. There is competition amongst peptides for access to an MHC Class II groove and it has been hypothesised that DM functions as a 'peptide editor' that catalyzes the replacement of one peptide for another within the groove. It is established that the DM catalyst interacts directly with the MHC Class II but the precise location of the interface is unknown. Here, we combine previously described mutational data with molecular docking and energy minimisation simulations to identify a putative interaction site of >4000A2 which agrees with known point mutational data for both the DR and DM molecule. The docked structure is validated by comparison with experimental data and previously determined properties of protein-protein interfaces. A possible dissociation mechanism is suggested by the presence of an acidic cluster near the N terminus of the bound peptide.
人类白细胞抗原（HLA）-DM是抗原呈递过程中的关键参与者，它催化II类相关恒定链衍生肽（CLIP）与主要组织相容性复合体（MHC）II类分子解离。肽段之间存在竞争以进入MHC II类凹槽，并且据推测，DM作为“肽段编辑器”发挥作用，催化凹槽内一种肽段被另一种肽段取代。已确定DM催化剂直接与MHC II类相互作用，但界面的精确位置尚不清楚。在此，我们将先前描述的突变数据与分子对接和能量最小化模拟相结合，以确定一个大于4000 Ų的假定相互作用位点，这与DR和DM分子的已知点突变数据一致。通过与实验数据和先前确定的蛋白质-蛋白质界面特性进行比较，验证了对接结构。结合肽段N端附近存在酸性簇，提示了一种可能的解离机制。
