The Carboxy Terminus of the Ligand Peptide Determines the Stability of the MHC Class I Molecule H-2Kb: A Combined Molecular Dynamics and Experimental Study.
The Carboxy Terminus of the Ligand Peptide Determines the Stability of the MHC Class I Molecule H-2Kb: A Combined Molecular Dynamics and Experimental Study.
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DOI：
10.1371/journal.pone.0135421
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Springer S
中科院分区：
文献类型：
--
作者：
Abualrous ET;Saini SK;Ramnarayan VR;Ilca FT;Zacharias M;Springer S
主要组织相容性复合体（MHC）I类分子（蛋白质）结合8至10个氨基酸的肽，以将它们呈递到细胞毒性T细胞的细胞表面。I类结合沟通过与肽末端的氢键以及通过与肽的锚残基侧链的多种相互作用结合肽。为了阐明这些相互作用是最重要的肽结合状态的热力学和动力学稳定性，我们结合了分子动力学模拟和实验方法在调查的构象动力学和结合参数的小鼠I类分子（H-2Kb）的最佳和截短的天然肽表位。我们表明，F口袋区占主导地位的结合沟的构象和热力学性质，因此，结合肽的C末端的F口袋区发挥了至关重要的作用，使肽结合状态的MHC I类。
Major histocompatibility complex (MHC) class I molecules (proteins) bind peptides of eight to ten amino acids to present them at the cell surface to cytotoxic T cells. The class I binding groove binds the peptide via hydrogen bonds with the peptide termini and via diverse interactions with the anchor residue side chains of the peptide. To elucidate which of these interactions is most important for the thermodynamic and kinetic stability of the peptide-bound state, we have combined molecular dynamics simulations and experimental approaches in an investigation of the conformational dynamics and binding parameters of a murine class I molecule (H-2Kb) with optimal and truncated natural peptide epitopes. We show that the F pocket region dominates the conformational and thermodynamic properties of the binding groove, and that therefore the binding of the C terminus of the peptide to the F pocket region plays a crucial role in bringing about the peptide-bound state of MHC class I.