Recognition of a CXCR4 sulfotyrosine by the chemokine stromal cell-derived factor-1α (SDF-1α/CXCL12)
Recognition of a CXCR4 sulfotyrosine by the chemokine stromal cell-derived factor-1α (SDF-1α/CXCL12)
复制标题
DOI：
10.1016/j.jmb.2006.04.052
复制
发表时间：
2006-06-23
影响因子：
5.6
通讯作者：
Volkman, Brian F.
中科院分区：
文献类型：
--
作者：
Veldkamp, Christopher T.;Seibert, Christoph;Volkman, Brian F.
趋化因子受体 CXCR4 的酪氨酸硫酸化增强了其与趋化因子 SDF-1 α 的相互作用。鉴于其他受体（包括 CCR5、CX3CR1 和 CCR2b）的类似翻译后修饰，酪氨酸硫酸化可能在趋化因子信号传导中具有普遍重要性。七个跨膜趋化因子受体的 N 端结构域已用于趋化因子-受体相互作用的结构研究，但从未在已知影响功能的适当翻译后修饰的背景下进行。在 21 位被表达的酪氨酰蛋白磺基转移酶 1 修饰的 CXCR4 肽和未修饰的肽在溶液中均无序，但以低微摩尔亲和力结合 SDF-1 α。 NMR和荧光偏振测量表明CXCR4肽稳定二聚体SDF-1α，并且磺基酪氨酸21结合趋化因子上包括精氨酸47的特定位点。我们得出结论，SDF-1α二聚体优先与受体肽相互作用，并且CXCR4最N端区域之外的残基（包括磺基酪氨酸21）与趋化因子配体进行特异性接触。 (c) 2006 Elsevier Ltd. 保留所有权利。
Tyrosine sulfation of the chemokine receptor CXCR4 enhances its interaction with the chemokine SDF-1 alpha. Given similar post-translational modification of other receptors, including CCR5, CX3CR1 and CCR2b, tyrosine sulfation may be of universal importance in chemokine signaling. N-terminal domains from seven transmembrane chemokine receptors have been employed for structural studies of chemokine-receptor interactions, but never in the context of proper post-translational modifications known to affect function. A CXCR4 peptide modified at position 21 by expressed tyrosylprotein sulfotransferase-1 and unmodified peptide are both disordered in solution, but bind SDF-1 alpha with low micromolar affinities. NMR and fluorescence polarization measurements showed that the CXCR4 peptide stabilizes dimeric SDF-1 alpha, and that sulfotyrosine 21 binds a specific site on the chemokine that includes arginine 47. We conclude that the SDF-1 alpha dimer preferentially interacts with receptor peptide, and residues beyond the extreme N-terminal region of CXCR4, including sulfotyrosine 21, make specific contacts with the chemokine ligand. (c) 2006 Elsevier Ltd. All rights reserved.