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首页> 外文期刊>Journal of Molecular Biology >Thermodynamics of Peptide Binding to the Transporter Associated with Antigen Processing (TAP).
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Thermodynamics of Peptide Binding to the Transporter Associated with Antigen Processing (TAP).

机译：肽与转运蛋白结合的热力学与抗原加工（TAP）。

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摘要

The ATP-binding cassette (ABC) transporter TAP plays an essential role in antigen processing and immune response to infected or malignant cells. TAP translocates proteasomal degradation products from the cytosol into the endoplasmic reticulum, where MHC class I molecules are loaded with these peptides. Kinetically stable peptide-MHC complexes are transported to the cell surface for inspection by cytotoxic T lymphocytes. The transport cycle of TAP is initiated by peptide binding, which is responsible for peptide selection and for stimulation of ATP-hydrolysis and subsequent translocation. Here we have analysed the driving forces for the formation of the peptide-TAP complex by kinetic and thermodynamic methods. First, the apparent peptide association and dissociation rates were determined at various temperatures. Strikingly, very high activation energies for apparent association (E(a)(ass)=106kJmol(-1)) and dissociation (E(a)(diss)=80kJmol(-1)) of the peptide-TAP complex were found. Next, the temperature-dependence of the peptide affinity constants was investigated by equilibrium-binding assays. Along with calculations of free enthalpy DeltaG, enthalpy DeltaH and entropy DeltaS, a large positive change in heat capacity was resolved (DeltaC degrees =23kJmol(-1)K(-1)), indicating a fundamental structural reorganization of the TAP complex upon peptide binding. The inspection of the conformational entropy reveals that approximately one-fourth of all TAP residues is rearranged. These thermodynamic studies indicate that at physiological temperature, peptide binding is endothermic and driven by entropy.
机译：ATP结合盒（ABC）转运蛋白TAP在抗原加工和对感染或恶性细胞的免疫应答中起着至关重要的作用。 TAP将蛋白酶体降解产物从胞质溶胶中转移到内质网中，其中MHC I类分子中装有这些肽。运动稳定的肽-MHC复合物被运输到细胞表面，以通过细胞毒性T淋巴细胞进行检查。 TAP的运输周期是由肽结合开始的，肽结合负责肽的选择以及刺激ATP水解和随后的转运。在这里，我们通过动力学和热力学方法分析了形成肽-TAP复合物的驱动力。首先，在各种温度下确定表观肽缔合和解离速率。令人惊讶的是，发现了肽-TAP复合物的表观缔合（E（a）（ass）= 106kJmol（-1））和解离（E（a）（diss）= 80kJmol（-1））很高的活化能。接下来，通过平衡结合试验研究了肽亲和常数的温度依赖性。连同自由焓DeltaG，焓DeltaH和熵DeltaS的计算，热容量的大正变化得到解决（DeltaC度= 23kJmol（-1）K（-1）），表明TAP复合物在肽上的基本结构重组捆绑。对构象熵的检查表明，所有TAP残基中大约四分之一被重新排列。这些热力学研究表明，在生理温度下，肽结合是吸热的，并且受熵驱动。

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