| 单体 C 反应蛋白与配体的互作机制研究 |
| Alternative Title | Research on mechanism of interaction between monomeric C-reactive Protein and ligands
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| 孟帆 |
| Thesis Advisor | 武一
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| 2014-05-27
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| Degree Grantor | 兰州大学
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| Place of Conferral | 兰州
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| Degree Name | 硕士
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| Keyword | C反应蛋白
肽段
配体
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| Abstract | 作为经典的急性期蛋白，C 反应蛋白（CRP）不仅是预示将来心血管事件强有力的标志物，也是调节动脉粥样硬化心血管疾病发病机理的直接参与者。 CRP存在两种异构体，天然五聚体 CRP（pCRP）和单体 CRP（mCRP），最近的研究发现在体内存在 pCRP 向 mCRP 解离的过程，预示着 CRP 有可能通过 mCRP 参与局部区域化病理过程。CRP 可与多种自体和外源配体作用，在机体的天然免疫过程中起重要作用。因此，对 mCRP-配体互作机制的研究，为治疗炎症及动脉粥样硬化等疾病提供了一条新思路。
在本研究中，我们首先选定一些重要配体，分别测定与之结合的 mCRP 的半饱和浓度，随后在 mCRP 的半饱和结合下，利用源自 mCRP 的肽段对该结合进行干扰。结果发现，只有对应 mCRP 氨基酸序列 35-47 位的肽段（肽段 35-47）可以在较低浓度下明显抑制所有配体与 mCRP 的结合，而且该肽段与其它肽段的最大区别仅在于氨基酸序列的不同。因此，我们认为 mCRP 与配体的相互作用，最有可能是通过 mCRP 的 35-47 位氨基酸序列进行介导。然后，我们对肽段35-47 进行了一系列改造和修饰，继续干扰 mCRP 与配体相互作用，进一步发现在该肽段的介导过程中， N 端氨基酸起到更重要的作用，且将肽段内所有左旋氨基酸替换为右旋氨基酸后显著提高其竞争效率。 |
| Other Abstract | The classical acute-phase protein, C-reactive protein (CRP), is not only a strong
marker for predicting future cardiovascular events, but also a direct partaker that
mediates pathogenesis of atherosclerotic cardiovascular disease. CRP has two types of
isoforms: native pentameric CRP (pCRP) and monomeric CRP (mCRP). Recently
research identified a dissociation mechanism leading to a conformational change from
the pCRP to mCRP, suggesting that CRP participates in localized pathological process
via mCRP. CRP acts with various intrinsic and extrinsic ligands playing a vital role in
the innate immune system. Thus, research on mCRP-ligands interaction provides a
new method to cure diseases, such as inflammation and atherosclerosis.
In the present study, we first selected some important ligands which were tested
respectively of the half saturated concentration of binding between mCRP and ligands.
Then, in the condition of this half saturated binding, we used mCRP-derived peptides
to interrupt it. The results showed that only one peptide whose amino acid sequence
corresponds to the 35-47 position of mCRP (peptide 35-47) can obviously inhibit the
binding of mCRP to all ligands at low concentrations, and the biggest difference
among peptide 35-47 and other peptides is only the amino acid sequences. According
to the above, we believe that the interaction between mCRP and ligands is most likely
mediated by the 35-47 amino acid sequence of mCRP. Then, we transformed and
modified peptide 35-47 to keep on interrupt the interaction between mCRP and
ligands. We further found that N-terminal of peptide 35-47 is more important during
the interaction and after replacing L-amino-acids to D-amino-acids, its efficiency of
competition has been obviously improved. |
| URL | 查看原文
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| Language | 中文
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| Document Type | 学位论文
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| Identifier | https://ir.lzu.edu.cn/handle/262010/221594
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| Collection | 生命科学学院
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Recommended Citation
GB/T 7714 |
孟帆. 单体 C 反应蛋白与配体的互作机制研究[D]. 兰州. 兰州大学,2014.
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