Extended flexible linker structures in the complement chimaeric conjugate CR2-Ig by scattering, analytical ultracentrifugation and constrained modelling: implications for function and therapy.
Extended flexible linker structures in the complement chimaeric conjugate CR2-Ig by scattering, analytical ultracentrifugation and constrained modelling: implications for function and therapy.
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通过散射、分析超速离心和约束建模扩展补体嵌合缀合物 CR2-Ig 中的柔性接头结构：对功能和治疗的影响。
DOI：
10.1016/j.jmb.2005.11.050
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Perkins,StephenJ
中科院分区：
文献类型：
--
作者：
Gilbert,HannahE;Aslam,Mohammed;Guthridge,JoelM;Holers,VMichael;Perkins,StephenJ
补体受体 2（CR2；CD21）是补体激活的膜结合调节因子，由 15 或 16 个短补体重复 (SCR) 结构域组成。使用小鼠 IgG1 抗体的 Fc 片段设计重组糖基化人 CR2 SCR 1-2 结构域对，以创建包含主要配体结合结构域的嵌合 CR2-Ig。这种嵌合体具有作为补体抑制剂或免疫调节剂的治疗潜力。 X 射线和中子散射以及分析超速离心鉴定了其在溶液中的结构域结构，并与有争议的去糖基化 CR2 SCR 1-2 的折叠晶体结构进行了比较。 X射线和中子散射测定CR2-Ig的回转半径RG分别为5.39(±0.14)nm和5.29(±0.01)nm。 CR2-Ig的最大尺寸测定为17nm。通过中子散射和沉降平衡测定，CR2-Ig 的分子量范围在 101,000Da 至 107,000Da 之间，与序列推导值 106,600Da 非常吻合。沉降速度给出的沉降系数为4.49(±0.11)S。 CR2-Ig 的立体化学完整模型是根据 CR2 SCR 1-2 和小鼠 IgG1 Fc 片段的晶体结构构建的。两个 SCR 结构域和 Fc 片段通过随机构象肽连接。对 35,000 个可能的 CR2-Ig 模型的分析表明，只有那些两个 SCR 结构域围绕 Fc 片段以随机方向排列成开放 V 形的模型才能解释散射和沉降数据。不可能定义相对于 Fc 片段的 Fab 样片段的单一构象家族。这种灵活性归因于相对较长的接头序列以及 CR2-Ig 中不存在抗体轻链。建模还证实 CR2 SCR 1-2 的结构在溶液中比在晶体结构中延伸得更多。
Complement receptor 2 (CR2; CD21) is a membrane-bound regulator of complement activation, being comprised of 15 or 16 short complement repeat (SCR) domains. A recombinant glycosylated human CR2 SCR 1–2 domain pair was engineered with the Fc fragment of a mouse IgG1 antibody to create a chimaera CR2-Ig containing the major ligand binding domains. Such a chimaera has therapeutic potential as a complement inhibitor or immune modulator. X-ray and neutron scattering and analytical ultracentrifugation identified its domain structure in solution, and provided a comparison with controversial folded-back crystal structures for deglycosylated CR2 SCR 1–2. The radius of gyration RGof CR2-Ig was determined to be 5.39(±0.14) nm and 5.29(±0.01)nm by X-ray and neutron scattering, respectively. The maximum dimension of CR2-Ig was determined to be 17nm. The molecular mass of CR2-Ig ranged between 101,000Da and 107,000Da as determined by neutron scattering and sedimentation equilibrium, in good agreement with the sequence-derived value of 106,600Da. Sedimentation velocity gave a sedimentation coefficient of 4.49(±0.11)S. Stereochemically complete models for CR2-Ig were constructed from crystal structures for the CR2 SCR 1–2 and mouse IgG1 Fc fragments. The two SCR domains and the Fc fragment were joined by randomised conformational peptides. The analysis of 35,000 possible CR2-Ig models showed that only those models in which the two SCR domains were arranged in an open V-shape in random orientations about the Fc fragment accounted for the scattering and sedimentation data. It was not possible to define one single conformational family of Fab-like fragment relative to the Fc fragment. This flexibility is attributed to the relatively long linker sequence and the absence of the antibody light chain from CR2-Ig. The modelling also confirmed that the structure of CR2 SCR 1–2 is more extended in solution than in its crystal structure.
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影响因子：
4.4
作者：
T. Mosmann;H. Cherwinski;M. Bond;M. Giedlin;R. Coffman
通讯作者：
T. Mosmann;H. Cherwinski;M. Bond;M. Giedlin;R. Coffman
Interleukin-2 刺激静息人 T 淋巴细胞对同种异体、γ 干扰素处理的角质形成细胞的反应。
DOI：
10.1111/1523-1747.ep12460913
发表时间：
1987
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
V. Morhenn;V. Morhenn;B. Nickoloff;B. Nickoloff
通讯作者：
B. Nickoloff
特应性皮炎中表皮 II 类人类淋巴细胞抗原的表达：与实验性过敏性接触性皮炎的比较。
影响因子：
13.8
作者：
J. Barker;D. Macdonald
通讯作者：
D. Macdonald
干扰素-γ 在淋巴细胞皮肤运输中的作用，重点是分子和细胞粘附事件。
影响因子：
--
作者：
Nickoloff,BJ
通讯作者：
Nickoloff,BJ
角质形成细胞 HLA-DR 表达：与真皮淋巴细胞浸润的关系
影响因子：
4.1
作者：
J. Barker;J. Ophir;D. Macdonald
通讯作者：
D. Macdonald