Bouzida D, Garnier J, Brower R, Cornette J, DeLisi C
Department of Biomedical Engineering, Boston University, Massachusetts 02215.
Protein Sci. 1994 Jun;3(6):911-9. doi: 10.1002/pro.5560030606.
Peptide recognition by class I products of the major histocompatibility complex requires association of the class I heavy chain with beta 2-microglobulin. We present results of Monte Carlo simulations of the beta-pleated sheet floor of the human class I MHC molecule, HLA-A2, with and without beta 2-microglobulin. We find a significant effect of beta 2-microglobulin on the side chains of residues near a region that would accommodate the C-terminus of a bound peptide. By modeling simultaneously each loop and its neighboring strand at either end of the class I cleft, we find that beta 2-microglobulin restricts the conformational space of residues that are central to binding peptides. The effect is most pronounced for R97 and H114 and somewhat less important for Y99 and Y116, the latter forming strong hydrogen bonds with neighboring residues in the heavy chain itself.
主要组织相容性复合体I类产物对肽的识别需要I类重链与β2-微球蛋白结合。我们展示了对人类I类MHC分子HLA - A2的β折叠片层底部进行的蒙特卡罗模拟结果，模拟了有和没有β2-微球蛋白的情况。我们发现β2-微球蛋白对靠近可容纳结合肽C末端区域附近残基的侧链有显著影响。通过同时对I类裂隙两端的每个环及其相邻链进行建模，我们发现β2-微球蛋白限制了对结合肽至关重要的残基的构象空间。这种影响在R97和H114处最为明显，而对Y99和Y116的影响稍小，后者在重链自身中与相邻残基形成强氢键。
