Hoover D M, Mizoue L S, Handel T M, Lubkowski J
Macromolecular Crystallography Laboratory, Program in Structural Biology, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA.
J Biol Chem. 2000 Jul 28;275(30):23187-93. doi: 10.1074/jbc.M002584200.
Fractalkine, or neurotactin, is a chemokine that is present in endothelial cells from several tissues, including brain, liver, and kidney. It is the only member of the CX(3)C class of chemokines. Fractalkine contains a chemokine domain (CDF) attached to a membrane-spanning domain via a mucin-like stalk. However, fractalkine can also be proteolytically cleaved from its membrane-spanning domain to release a freely diffusible form. Fractalkine attracts and immobilizes leukocytes by binding to its receptor, CX(3)CR1. The x-ray crystal structure of CDF has been solved and refined to 2.0 A resolution. The CDF monomers form a dimer through an intermolecular beta-sheet. This interaction is somewhat similar to that seen in other dimeric CC chemokine crystal structures. However, the displacement of the first disulfide in CDF causes the dimer to assume a more compact quaternary structure relative to CC chemokines, which is unique to CX(3)C chemokines. Although fractalkine can bind to heparin in vitro, as shown by comparison of electrostatic surface plots with other chemokines and by heparin chromatography, the role of this property in vivo is not well understood.
趋化因子，即神经趋化蛋白，是一种存在于包括脑、肝和肾在内的多种组织的内皮细胞中的趋化因子。它是CX(3)C类趋化因子的唯一成员。趋化因子包含一个通过粘蛋白样柄连接到跨膜结构域的趋化因子结构域（CDF）。然而，趋化因子也可以从其跨膜结构域被蛋白水解切割，以释放一种可自由扩散的形式。趋化因子通过与其受体CX(3)CR1结合来吸引并固定白细胞。CDF的X射线晶体结构已被解析并精修至2.0埃分辨率。CDF单体通过分子间β折叠形成二聚体。这种相互作用与其他二聚体CC趋化因子晶体结构中的相互作用有些相似。然而，CDF中第一个二硫键的位移导致二聚体相对于CC趋化因子呈现出更紧凑的四级结构，这是CX(3)C趋化因子所特有的。尽管如通过与其他趋化因子的静电表面图比较以及肝素色谱法所示，趋化因子在体外可与肝素结合，但其在体内的这种特性的作用尚不清楚。
