Dimeric structure of the coxsackievirus and adenovirus receptor D1 domain at 1.7 Å resolution
Dimeric structure of the coxsackievirus and adenovirus receptor D1 domain at 1.7 Å resolution
复制标题
DOI：
10.1016/s0969-2126(00)00528-1
复制
发表时间：
2000-11-15
期刊：
影响因子：
5.7
通讯作者：
Cusack, S
中科院分区：
文献类型：
--
作者：
van Raaij, MJ;Chouin, E;Cusack, S
背景：柯萨奇病毒和腺病毒受体（CAR）包含两个胞外免疫球蛋白结构域、一个跨膜螺旋和一个C端胞内结构域。 CAR 的氨基末端免疫球蛋白结构域 (D1) 对于腺病毒结合是必要且充分的，而柯萨奇病毒附着位点尚未定位。尽管最近提出 CAR 作为血友病细胞粘附分子发挥作用，但 CAR 的正常细胞作用目前尚不清楚。 结果：人 CAR D1 结构域通过细菌表达并结晶。使用与腺病毒12型纤维头结合的CAR D1的结构通过分子替换来解析该结构，并将分辨率细化至1.7埃，包括单独的各向异性温度因素。除了参与纤维头结合和晶体中同源二聚化的 BC、C"D 和 FG 环之外，两个 CAR D1 结构实际上是相同的。分析平衡超速离心显示溶液中也存在二聚体，解离常数为 16 muM。结论：CAR D1 结构域使用与腺病毒纤维头相互作用的相同 GFCC'C" 表面在晶体中形成同源二聚体。同二聚体与 CD2 D1-CD58 D1 异二聚体非常相似。 CAR D1 还在溶液中形成具有其他细胞粘附复合物典型解离常数的二聚体。这些结果与 CAR 在发育中的小鼠大脑中可能作为同种细胞粘附分子的生理功能的报道一致。因此，腺病毒可能招募了 CAR 现有且保守的相互作用表面，用于其自身的细胞附着。
Background: The coxsackievirus and adenovirus receptor (CAR) comprises two extracellular immunoglobulin domains, a transmembrane helix and a C-terminal intracellular domain. The amino-terminal immunoglobulin domain (D1) of CAR is necessary and sufficient for adenovirus binding, whereas the site of coxackievirus attachment has not yet been localized. The normal cellular role of CAR is currently unknown, although CAR was recently proposed to function as a hemophilic cell adhesion molecule.Results: The human CAR D1 domain was bacterially expressed and crystallized. The structure was solved by molecular replacement using the structure of CAR D1 bound to the adenovirus type 12 fiber head and refined to 1.7 Angstrom resolution, including individual anisotropic temperature factors. The two CAR D1 structures are virtually identical, apart from the BC, C"D, and FG loops that are involved both in fiber head binding and homodimerization in the crystal. Analytical equilibrium ultracentrifugation shows that a dimer also exists in solution, with a dissociation constant of 16 muM.Conclusions: The CAR D1 domain forms homodimers in the crystal using the same GFCC'C" surface that interacts with the adenovirus fiber head. The homodimer is very similar to the CD2 D1-CD58 D1 heterodimer. CAR D1 also forms dimers in solution with a dissociation constant typical of other cell adhesion complexes. These results are consistent with reports that CAR may function physiologically as a homophilic cell adhesion molecule in the developing mouse brain. Adenovirus may thus have recruited an existing and conserved interaction surface of CAR to use for its own cell attachment.