Hannan J, Young K, Szakonyi G, Overduin M J, Perkins S J, Chen X, Holers V M
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
Biochem Soc Trans. 2002 Nov;30(Pt 6):983-9. doi: 10.1042/bst0300983.
Using X-ray crystallography, we have determined the structure of the first two short consensus repeats (SCRs) of human complement receptor (CR) 2 in complex with C3d. These studies revealed: (i) a primary site of interaction for C3d within SCR2 of CR2, (ii) a hydrophobic patch holding SCR1 to SCR2 in a rigid V-shape, (iii) a dimer formed by interactions between SCR1 of each molecule, (iv) several non-linear sequences on C3d that interact with CR2 and (v) mutations of C3d amino acids within the co-crystal interface that resulted in decreased binding. In addition, a polymorphism that results in decreased C3d binding and introduces a new glycosylation site predicted to disrupt the dimer interface was found in the New Zealand White autoimmune mouse strain. Although the co-crystal complex results are in agreement with a subset of prior studies, our additional findings, which demonstrate an extended SCR1-SCR2 structure in solution and differences in the kinetics of ligand-receptor interactions with longer forms of CR2, have suggested a more complex receptor-ligand interaction. To characterize this interaction further, several approaches directed at the determination of solution phase interactions as well as the analysis of the three-dimensional structure of CR2 alone and key CR2 mutants will be necessary.
通过X射线晶体学，我们确定了人补体受体（CR）2的前两个短共有重复序列（SCR）与C3d形成复合物的结构。这些研究揭示了：（i）CR2的SCR2内C3d的主要相互作用位点；（ii）一个疏水区域将SCR1和SCR2以刚性V形固定在一起；（iii）由每个分子的SCR1之间的相互作用形成的二聚体；（iv）C3d上与CR2相互作用的几个非线性序列；（v）共晶体界面内C3d氨基酸的突变导致结合力下降。此外，在新西兰白色自身免疫小鼠品系中发现了一种多态性，该多态性导致C3d结合力下降，并引入了一个预计会破坏二聚体界面的新糖基化位点。尽管共晶体复合物的结果与先前的一部分研究一致，但我们的其他发现表明溶液中存在扩展的SCR1-SCR2结构，并且配体-受体与更长形式的CR2相互作用的动力学存在差异，这提示了一种更复杂的受体-配体相互作用。为了进一步表征这种相互作用，需要采取几种方法来确定溶液相相互作用以及单独分析CR2和关键CR2突变体的三维结构。
