Crystal structure of human CD38 extracellular domain
Crystal structure of human CD38 extracellular domain
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DOI：
10.1016/j.str.2005.05.012
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发表时间：
2005-09-01
期刊：
影响因子：
5.7
通讯作者：
Hao, Q
中科院分区：
文献类型：
--
作者：
Liu, Q;Kriksunov, IA;Hao, Q
人CD38是一种多功能蛋白质，参与多种功能。作为一种酶，它负责合成两种钙信使cADPR和NAADP；作为一种抗原，它参与调节细胞的黏附、分化和增殖。CD38是HIV-1感染进展的标志物，也是B-CLL的阴性预后标志物。我们已经确定了人CD38的可溶胞外域的晶体结构，分辨率为1.9埃。该酶的总体拓扑结构类似于相关蛋白CD157和海藻ADP-核糖环化酶，但在两个末端有较大的结构变化。延伸的带正电荷的N末端与结晶学不对称单元中的另一个CD38分子具有侧向结合。对CD38底物结合模型的分析揭示了两个关键残基，它们可能是控制CD38‘S NAD水解酶、腺苷二磷酸核糖环酶和cADPR水解酶活性的关键残基。
Human CD38 is a multifunctional protein involved in diverse functions. As an enzyme, it is responsible for the synthesis of two Ca2+ messengers, cADPR and NAADP; as an antigen, it is involved in regulating cell adhesion, differentiation, and proliferation. Besides, CD38 is a marker of progression of HIV-1 infection and a negative prognostic marker of B-CLL. We have determined the crystal structure of the soluble extracellular domain of human CD38 to 1.9 angstrom resolution. The enzyme's overall topology is similar to the related proteins CD157 and the Aplysia ADP-ribosyl cyclase, except with large structural changes at the two termini. The extended positively charged N terminus has lateral associations with the other CD38 molecule in the crystallographic asymmetric unit. The analysis of the CD38 substrate binding models revealed two key residues that may be critical in controlling CD38's multifunctionality of NAD hydrolysis, ADP-ribosyl cyclase, and cADPR hydrolysis activities.