CRYSTALLOGRAPHIC STUDIES OF HUMAN CD38 MULTIFUNCTIONAL ECTOZYME

人CD38多功能胞外酶的晶体学研究

• 批准号: 6119535
• 负责人: SRIDHAR G PRASAD
• 金额: --
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2000-04-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6119535
• 关键词: biomaterials; proteins; structural biology

CD38 is a human lymphocyte differentiation antigen and multifunctional surface receptor with both enzymatic and cell adhesion functions. Ligation of CD38 with agonistic antibodies induces diverse effects in hematopoietic cells. As an enzyme CD38 synthesizes cADPR from NAD and hydrolyzes cADPR to ADPR. The existence of a transmembrane cell surface glycoprotein, which is both a receptor and an enzyme, presents an intriguing and as yet unanswered question: What is the function of this ectozyme? In B-cells CD38 functions as a co-receptor for BCR signaling. CD38 may also mediate ADP ribosylation of cell surface proteins as well as regulating insulin secretion and interacting with CD31 and the CD3/TCR complex. A structural investigation of CD38 is essential to understand the immunological significance of this multifunctional molecule. We seek time on BL 9-1/7-1 in order to collect high-resolution native data and heavy atom derivative data sets for initial structure determination and to subsequently elucidate the catalytic mechanism. A previous test done on BL 7-1 with a tiny crystal resulted in diffraction to almost 2.8 E. Beam time on BL 9-1/7-1 is requested in order to attain a high resolution structure to comprehend the reaction mechanism of CD38.

CD 38是人淋巴细胞分化抗原， 具有酶和细胞粘附的多功能表面受体 功能协调发展的 CD 38与激动性抗体的连接诱导了多种多样的 对造血细胞的影响。 作为一种酶，CD 38合成cADPR 将cADPR水解为ADPR。 的存在 跨膜细胞表面糖蛋白，其既是受体， 一种酶，提出了一个有趣的，但尚未回答的问题： 这种胞外酶的功能是什么？ 在B细胞中，CD 38起着 BCR信号传导的辅助受体。 CD 38也可能介导ADP核糖基化 以及调节胰岛素分泌， 与CD 31和CD 3/TCR复合物相互作用。 结构 CD 38的研究对于了解免疫学 这个多功能分子的重要性。 我们在BL上寻找时间 9-1/7-1为了收集高分辨率的原生数据和重原子 用于初始结构确定的衍生数据集， 随后阐明了催化机理。 之前的测试 在BL 7-1上用一个小的晶体产生了几乎2.8E的衍射。 需要BL 9-1/7-1上的射束时间才能达到高水平 解析结构以理解CD 38的反应机制。