(E) - 和乙烯异大大改变了II类MHC A(q) /糖复合体中的结网,并影响了T细胞的识别
Ida E Andersson1, Tsvetelina Batsalova, Sabrina Haag
1Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden.
Journal of the American Chemical Society
|July 20, 2011
概括
研究抗原呈现中的键揭示了修改如何影响它们与II类主要基因相容性复合体 (MHC) 蛋白质的结合,这对自身免疫性疾病研究至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
- 计算化学计算化学
背景情况:
- 通过II类主要组织相容性复合体 (MHC) 蛋白向CD4(+) T细胞呈现抗原对于免疫反应和理解自身免疫性疾病至关重要.
- MHC II 类分子和之间的相互作用是治疗干预的关键目标.
研究的目的:
- 研究键在糖与关节炎相关的小鼠A(q) 类II MHC蛋白的结合中所起的作用.
- 探索使用 (E) - 和乙烯氨基胺-键同位素的特定结构修改对-MHC结合动态的影响.
主要方法:
- 合成异基修饰的CII259-270糖.
- 实验性确定对改性糖的A(q) 结合亲缘关系.
- 分子动力学 (MD) 模拟来分析键网络和构造变化.
主要成果:
- 异基修饰导致了A(q) 结合亲和力的显著和多样化的损失.
- MD模拟显示了动态键形成和网络内的强合,N端修改具有明显的影响.
- 一种乙烯异异出乎意料地表现出比 (E) - 更强的结合,与其他观察到的趋势相反,由于改变了构造和相互作用.
结论:
- 键的动态性质和相互连接对于II类MHC-相互作用至关重要.
- 结构性修改,特别是在N端区域,深刻影响结和T细胞受体参与.
- 了解这些动态相互作用对于设计针对自身免疫性疾病的向疗法至关重要.
相关概念视频
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Alkenes like 1-butene and 2-butene exhibit constitutional isomerism, as they differ in the position of the double bond. Further, 2-butene exhibits stereoisomerism and exists as two distinct compounds differing in spatial arrangement.
An isomer is called cis-2-butene when the methyl groups are on the same side of the double bond, and the other stereoisomer, in which methyl groups are on the opposite side of the double bond, is called trans-2-butene. The cis and trans stereoisomers are not...
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When a substrate with two different β hydrogens undergoes an E2 elimination, the presence of a strong base can yield two regioisomeric alkenes. The more-substituted alkene is the major product and...
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An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
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The relative stability of alkenes can be determined by comparing their heats of hydrogenation. The lower heat of hydrogenation indicates the more stable alkene. The three main factors determining the relative stability of alkenes are i) the number of substituents attached to the double-bond carbon atoms, ii) hyperconjugation, and iii) the stereochemistry of the double bond.
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Olefins, which are unsaturated hydrocarbons containing one or more carbon–carbon double bonds, are broadly divided into alkenes and cycloalkenes. The general chemical formula of an alkene is CnH2n.
Doubly bonded carbons are sp2 hybridized and have a trigonal planar geometry. The double bond is composed of a σ bond formed by the overlap of hybrid orbitals and a π bond produced by the lateral overlap of unhybridized 2p orbitals on both the carbons. Each carbon atom is bonded to two hydrogen atoms...
Doubly bonded carbons are sp2 hybridized and have a trigonal planar geometry. The double bond is composed of a σ bond formed by the overlap of hybrid orbitals and a π bond produced by the lateral overlap of unhybridized 2p orbitals on both the carbons. Each carbon atom is bonded to two hydrogen atoms...


