Laboratoire de Cristallogenese et Cristallographie des Protéines, Institut de Biologie Structurale Jean-Pierre Ebel, Commissariat à l'Energie Atomique, Centre National de la Recherche Scientifique, Université Joseph Fourier, Grenoble, France.
J Immunol. 2010 Jul 15;185(2):808-12. doi: 10.4049/jimmunol.1000184. Epub 2010 Jun 14.
C1q, the recognition subunit of the C1 complex of complement, is an archetypal pattern recognition molecule with the striking ability to sense a wide variety of targets, including a number of altered self-motifs. The recognition properties of its globular domain were further deciphered by means of x-ray crystallography using deoxy-D-ribose and heparan sulfate as ligands. Highly specific recognition of deoxy-D-ribose, involving interactions with Arg C98, Arg C111, and Asn C113, was observed at 1.2 A resolution. Heparin-derived tetrasaccharide interacted more loosely through Lys C129, Tyr C155, and Trp C190. These data together with previous findings define a unique binding area exhibiting both polyanion and deoxy-D-ribose recognition properties, located on the inner face of C1q. DNA and heparin compete for C1q binding but are poor C1 activators compared with immune complexes. How the location of this binding area in C1q may regulate the level of C1 activation is discussed.
C1q 是补体 C1 复合物的识别亚基，是一种典型的模式识别分子，具有识别广泛靶标的惊人能力，包括许多自身改变的基序。其球形结构域的识别特性通过使用脱氧-D-核糖和硫酸乙酰肝素作为配体的 X 射线晶体学进一步阐明。在 1.2A 分辨率下观察到高度特异性识别脱氧-D-核糖，涉及与 Arg C98、Arg C111 和 Asn C113 的相互作用。肝素衍生的四糖通过 Lys C129、Tyr C155 和 Trp C190 更松散地相互作用。这些数据与之前的发现一起定义了一个独特的结合区域，该区域同时具有多阴离子和脱氧-D-核糖的识别特性，位于 C1q 的内表面。与免疫复合物相比，DNA 和肝素竞争与 C1q 的结合，但作为 C1 的激活物较差。该结合区域在 C1q 中的位置如何调节 C1 激活水平的问题正在讨论中。
