The crystal structure of the costimulatory OX40-OX40L complex
The crystal structure of the costimulatory OX40-OX40L complex
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DOI：
10.1016/j.str.2006.06.015
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发表时间：
2006-08-01
期刊：
影响因子：
5.7
通讯作者：
Hymowitz, Sarah G.
中科院分区：
文献类型：
--
作者：
Compaan, Deanne M.;Hymowitz, Sarah G.
OX 40是由OX 40 L激活的T细胞共刺激分子。阻断OX 40 L-OX 40相互作用在T细胞病理学的动物模型中具有改善作用。为了更好地理解OX 40和OX 40 L之间的相互作用，我们分别在1.45和2.4埃下测定了鼠OX 40 L和人OX 40-OX 40 L复合物的晶体结构。这些结构表明，OX 40 L是肿瘤坏死因子超家族（TNFSF）中一个非常小的成员。形成功能性三聚体的OX 40 L原聚体的排列是非典型的，并且与其他成员的排列不同之处在于每个原聚体相对于三聚体轴旋转15 °，导致开放式组装。OX 40 L的界面残基的定点变化表明该界面缺乏单个“热点”，相反，结合能分散在至少两个不同的区域。这些结构证明了TNFSF成员的结构可塑性及其与受体的相互作用。
OX40 is a T cell costimulator activated by OX40L. Blockade of the OX40L-OX40 interaction has ameliorative effects in animal models of T cell pathologies. In order to better understand the interaction between OX40 and OX40L, we have determined the crystal structure of murine OX40L and of the human OX40-OX40L complex at 1.45 and 2.4 angstrom, respectively. These structures show that OX40L is an unusually small member of the tumor necrosis factor superfamily (TNFSF). The arrangement of the OX40L protomers forming the functional trimer is atypical and differs from that of other members by a 15, rotation of each protomer with respect to the trimer axis, resulting in an open assembly. Site-directed changes of the interfacial residues of OX40L suggest this interface lacks a single "hot spot" and that instead, binding energy is dispersed over at least two distinct areas. These structures demonstrate the structural plasticity of TNFSF members and their interactions with receptors.