Chapter 4 │ Page 133 For the interaction between HLA-E and CD94, the most notable change in the oxidized state is a weaker binding of the salt bridge Arg168CD94 – Asp68HLA-E, as evidenced by the 21% decrease in binding persistence. Some of the salt bridges that contribute to the interaction between HLA-E and NKG2A seemingly exhibit a decrease in binding for the oxidized state as well, though this is mostly accompanied by an increase in binding to another amino acid close by. The reduced binding of Asp162HLA-E to Arg215NKG2A is accompanied by an enhanced binding to Lys199NKG2A, while the lower binding of Lys217NKG2A to Glu161HLA-E coincides with increased binding to Asp162HLA-E. Finally, the binding of salt bridge Lys199NKG2A – Glu166HLA-E is increased for the oxidized complex. However, unlike for the other salt bridges, this changed behavior was present in only one simulation replicate in which this interaction was very significant, while not being significantly present (<10%) in any of the other replicates. Compared to NKG2A/CD94, KIR receptors have a smaller interaction surface with MHC-I molecules. This is accompanied by fewer interactions between the receptor and its ligand, which is reflected in the lower calculated binding energy (Figure 5). The interaction between HLA-Cw4 and KIR2DL1 is again dominated by polar interactions, including three salt bridges that are found in the crystal structure of the complex [42]. Two of these salt bridges (Asp135KIR2DL1 – Arg145HLA-Cw4 and Asp183KIR2DL1 – Lys146HLA-Cw4) are conserved across HLA-C molecules, while the third (Glu187KIR2DL1 – Lys80HLA-Cw4) is unique to KIR2DL1, and plays an especially important role in the binding of this complex [38]. As shown in Table 4, the oxidation of HLA-Cw4 was found to a ect these salt bridges in di erent ways. The Glu187KIR2DL1 – Lys80HLA-Cw4 salt bridge was calculated to have an increased binding persistence, implying a stronger interaction. Meanwhile, the binding of the other two salt bridges decreases. Both distance changes correspond logically to the observed pivot of oxidized HLA-Cw4 with respect to KIR2DL1, shown earlier in Figure 3. When looking at the calculated binding free energy, these e ects (i.e.
RkJQdWJsaXNoZXIy MTk4NDMw