The 15 SCR flexible extracellular domains of human complement receptor type 2 can mediate multiple ligand and antigen interactions
The 15 SCR flexible extracellular domains of human complement receptor type 2 can mediate multiple ligand and antigen interactions
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DOI：
10.1016/j.jmb.2006.08.012
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发表时间：
2006-10-06
影响因子：
5.6
通讯作者：
Perkins, Stephen J.
中科院分区：
文献类型：
--
作者：
Gilbert, Hannah E.;Asokan, Rengasamy;Perkins, Stephen J.
2 型补体受体（CR2、CD21）是一种细胞表面蛋白，在 B 细胞激活过程中将先天性免疫反应和适应性免疫反应联系起来。 CR2 的胞外部分包含 15 或 16 个短补体调节器 (SCR) 结构域，其在溶液中的整体排列尚不清楚。这是通过约束散射和超速离心建模确定的。通过X射线和中子散射测定CR2 SCR 1-15的回转半径为11.5 nin，其横截面为1.8 nm。距离分布函数P(r)表明CR2 SCR 1-15的总长度为38圈。沉降平衡曲线拟合得到的平均分子量为 135,000 (+/- 13,000) Da，与完全糖基化的结构一致。使用 g*(s) 导数方法进行的速度实验给出了 4.2 (+/- 0.1) S 的沉降系数。为了构建用于约束拟合的 CR2 SCR 1-15 模型，将 15 个 SCR 结构域的同源模型与分子动力学模拟生成的随机连接肽相结合。使用自动化程序，对 15,000 个可能的 CR2 SCR 1-15 模型的分析表明，只有那些 15 个 SCR 域灵活但部分折回的模型才能解释散射和沉降数据。最适合的 CR2 模型为 CR2 与四种配体 C3d、CD23、gp350 和 IFN-α 的多功能相互作用提供了直观的解释。CR2 SCR 1-2 的灵活位置可能促进 C3d-抗原复合物与 B 细胞受体的相互作用。 (c) 2006 Elsevier Ltd. 保留所有权利。
Complement receptor type 2 (CR2, CD21) is a cell surface protein that links the innate and adaptive immune response during the activation of B cells. The extracellular portion of CR2 comprises 15 or 16 short complement regulator (SCR) domains, for which the overall arrangement in solution is unknown. This was determined by constrained scattering and ultracentrifugation modelling. The radius of gyration of CR2 SCR 1-15 was determined to be 11.5 nin by both X-ray and neutron scattering, and that of its cross-section was 1.8 nm. The distance distribution function P(r) showed that the overall length of CR2 SCR 1-15 was 38 rim. Sedimentation equilibrium curve fits gave a mean molecular weight of 135,000 (+/- 13,000) Da, in agreement with a fully glycosylated structure. Velocity experiments using the g*(s) derivative method gave a sedimentation coefficient of 4.2 ( +/- 0.1) S. In order to construct a model of CR2 SCR 1-15 for constrained fitting, homology models for the 15 SCR domains were combined with randomised linker peptides generated by molecular dynamics simulations. Using an automated procedure, the analysis of 15,000 possible CR2 SCR 1-15 models showed that only those models in which the 15 SCR domains were flexible but partially folded back accounted for the scattering and sedimentation data. The best-fit CR2 models provided a visual explanation for the versatile interaction of CR2 with four ligands C3d, CD23, gp350 and IFN-alpha.. The flexible location of CR2 SCR 1-2 is likely to facilitate interactions of C3d-antigen complexes with the B cell receptor. (c) 2006 Elsevier Ltd. All rights reserved.