Elucidation of the CCR1- and CCR5-binding modes of MIP-1α by application of an NMR spectra reconstruction method to the transferred cross-saturation experiments.
Elucidation of the CCR1- and CCR5-binding modes of MIP-1α by application of an NMR spectra reconstruction method to the transferred cross-saturation experiments.
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DOI：
10.1007/s10858-015-9992-x
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发表时间：
2015-12
影响因子：
2.7
通讯作者：
Shimada I
中科院分区：
文献类型：
--
作者：
Yoshiura C;Ueda T;Kofuku Y;Matsumoto M;Okude J;Kondo K;Shiraishi Y;Shimada I
C-C趋化因子受体1（CCR1）和CCR5参与多种炎症和免疫反应，并以不同方式调节自身免疫性疾病的进展。然而，在结合界面处鉴定的残基数量不足以阐明 CCR1 和 CCR5 与 MIP-1α 结合模式的差异，因为 CCR1 和 CCR5 样品的 NMR 测量时间限于 24 小时，因为它们的稳定性较低。在这里，我们将最近开发的 NMR 谱重建方法（FOuRier 分析中的实验数据守恒）应用于嵌入重建高密度脂蛋白和 MIP-1α 脂质双层中的趋化因子受体 CCR1 和 CCR5 的酰胺定向转移交叉饱和实验。我们的实验表明，MIP-1α N 环和 β 折叠上的残基与 CCR1 和 CCR5 接近，而 C 末端螺旋区域的残基与 CCR5 接近。这些结果表明，伴随 C 端螺旋区 E57 和 V63 残基取代的 MIP-1α 单核苷酸多态性的遗传影响，将为阐明 CCR5-MIP-1α 相互作用如何影响自身免疫性疾病的进展提供线索。本文的在线版本 (doi:10.1007/s10858-015-9992-x) 包含补充材料，可供授权用户使用。
C–C chemokine receptor 1 (CCR1) and CCR5 are involved in various inflammation and immune responses, and regulate the progression of the autoimmune diseases differently. However, the number of residues identified at the binding interface was not sufficient to clarify the differences in the CCR1- and CCR5-binding modes to MIP-1α, because the NMR measurement time for CCR1 and CCR5 samples was limited to 24 h, due to their low stability. Here we applied a recently developed NMR spectra reconstruction method, Conservation of experimental data in ANAlysis of FOuRier, to the amide-directed transferred cross-saturation experiments of chemokine receptors, CCR1 and CCR5, embedded in lipid bilayers of the reconstituted high density lipoprotein, and MIP-1α. Our experiments revealed that the residues on the N-loop and β-sheets of MIP-1α are close to both CCR1 and CCR5, and those in the C-terminal helix region are close to CCR5. These results suggest that the genetic influence of the single nucleotide polymorphisms of MIP-1α that accompany substitution of residues in the C-terminal helix region, E57 and V63, would provide clues toward elucidating how the CCR5–MIP-1α interaction affects the progress of autoimmune diseases. The online version of this article (doi:10.1007/s10858-015-9992-x) contains supplementary material, which is available to authorized users.
影响因子：
2.7
作者：
Ueda, Takumi;Yoshiura, Chie;Matsumoto, Masahiko;Kofuku, Yutaka;Okude, Junya;Kondo, Keita;Shiraishi, Yutaro;Takeuchi, Koh;Shimada, Ichio
通讯作者：
Shimada, Ichio