Tetrameric Interaction of the Ectoenzyme CD38 on the Cell Surface Enables Its Catalytic and Raft-Association Activities
Tetrameric Interaction of the Ectoenzyme CD38 on the Cell Surface Enables Its Catalytic and Raft-Association Activities
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DOI：
10.1016/j.str.2012.06.017
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发表时间：
2012-09-05
期刊：
影响因子：
5.7
通讯作者：
Yanagishita, Masaki
中科院分区：
文献类型：
--
作者：
Hara-Yokoyama, Miki;Kukimoto-Niino, Mutsuko;Yanagishita, Masaki
白细胞表面抗原CD 38是哺乳动物中主要的烟酰胺腺嘌呤二核苷酸糖水解酶，其胞外酶活性参与钙动员。CD 38也是一种筏依赖性信号分子。CD 38在细胞表面形成四聚体，但四聚体的结构基础和功能意义仍未被探索。我们确定的接口，通过在细胞表面上的位点特异性交联与扩展的遗传密码，基于晶体学分析的小鼠CD 38的嗜同性相互作用。这三个界面的组合使CD 38能够四聚化：一个涉及质膜α-螺旋的界面负责核心二聚体的形成，其通过其他两个界面进一步二聚化。这种二聚体的二聚化是CD 38在膜筏中的催化活性和定位所必需的。糖基化防止四聚体的进一步自缔合。因此，四聚体相互作用是CD 38多方面作用的基础。
The leukocyte cell-surface antigen CD38 is the major nicotinamide adenide dinucleotide glycohydrolase in mammals, and its ectoenzyme activity is involved in calcium mobilization. CD38 is also a raft-dependent signaling molecule. CD38 forms a tetramer on the cell surface, but the structural basis and the functional significance of tetramerization have remained unexplored. We identified the interfaces contributing to the homophilic interaction of mouse CD38 by site-specific crosslinking on the cell surface with an expanded genetic code, based on a crystallographic analysis. A combination of the three interfaces enables CD38 to tetramerize: one interface involving the juxtamembrane alpha-helix is responsible for the formation of the core dimer, which is further dimerized via the other two interfaces. This dimerization of dimers is required for the catalytic activity and the localization of CD38 in membrane rafts. The glycosylation prevents further self-association of the tetramer. Accordingly, the tetrameric interaction underlies the multifaceted actions of CD38.