Class I MHC is stabilized against thermal denaturation by physiological concentrations of NaCl
Class I MHC is stabilized against thermal denaturation by physiological concentrations of NaCl
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DOI：
10.1021/bi000442n
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发表时间：
2000-08-01
期刊：
影响因子：
2.9
通讯作者：
Collins, EJ
中科院分区：
文献类型：
--
作者：
Batalia, MA;Kirksey, TJ;Collins, EJ
I类MHC分子是由同种异型特异性重链、非共价结合的蛋白β（2）-微球蛋白（β（2）m）和肽组成的三元复合物。复合物通过一系列复杂的伴侣蛋白和肽装载机制在内质网中组装。在不存在β（2）m或肽的情况下，非常少的I类重链被转运到细胞表面。不包含蛋白质的所有三个部分的复合物在体内不能生产，在体外也根本不能生产。复合物在体外耐受热变性的能力已被证明与肽的结合亲和力有关。特别是，一些低亲和力的肽复合物在体外或低于人体基础体温下变性，但在体内是有效的生物制剂，在这里，我们表明，这些复合物是稳定的，对热变性的生理共溶剂，最大限度地稳定150 mM NaCl。虽然150 mM NaCl的稳定程度是最大的低亲和力肽/MHC复合物，稳定的机制是独立的肽序列。假设这种效应通过多种机制发生，包括增加β（2）m对复合物的亲和力和电荷屏蔽。
Class I MHC molecules are ternary complexes composed of an allotype specific heavy chain, a noncovalently associated protein beta(2)-microglobulin (beta(2)m), and a peptide. The complexes are assembled in the endoplasmic reticulum by a complex series of chaperones and peptide-loading mechanisms. In the absence of beta(2)m or peptide, very little class I heavy chain is transported to the surface of the cell. Complexes that do not contain all three parts of the protein are not made productively in vivo and not at all in vitro. The ability of the complex to withstand thermal denaturation in vitro has been shown to be related to the binding affinity of the peptide. Paradoxically, some low-affinity peptide complexes denature at or below human basal body temperatures in vitro but are effective biological agents in vivo, Here we show that these complexes are stabilized against thermal denaturation by physiological cosolvents and maximally stabilized by 150 mM NaCl. While the degree of stabilization by 150 mM NaCl is greatest for low-affinity peptide/MHC complexes, the mechanism of stabilization is independent of peptide sequence. This effect is hypothesized to occur by multiple mechanisms including increasing the affinity of beta(2)m for the complex and charge screening,.