A) 人源LanCL1三维结构的主链飘带示意图. 外围螺旋和内层螺旋分别显示红色和黄色. (B) 人源LanCL1的表面电势图. 球棍模型表示结合的谷胱甘肽. (C) 显示经过空pBI/eGFP vector或LanCL1野生型或各种突变体转染的PC12细胞用50 ng/ml NGF处理后四天的荧光显微图片.
近期，著名期刊《基因与发育》（Genes & Development）发表了中科院院士饶子和领导的中国科学院生物物理所/清华大学/南开大学联合实验室在人源LanCL1 (lanthionine synthetase C-like protein-1)蛋白研究上的最新研究成果，论文题为Structure of Human Lanthionine Synthetase C-like Protein 1 and Its Interaction with Eps8 and Glutathione。
人源LanCL1是一类功能研究较少的蛋白，与原核生物LanC (lanthionine cyclase）在序列上只有约15%的同源性。该实验室得到了人源LanCL1以及其与谷胱甘肽复合物的三维晶体结构。通过对该结构的分析，他们发现该蛋白有可能是一个能直接耦合细胞氧化还原状态与生长因子受体通路信号转导的分子。进一步的突变实验和体外SPR(表面等离子体共振技术)等实验证实人源LanCL1能特异性地结合生长因子信号传导相关的蛋白EPS8（生长因子受体底物蛋白8）上 的SH3 domain，并且这一相互作用受谷胱甘肽的调节。在此基础上，细胞实验也表明所有能减弱与EPS8相互作用的突变体均能抑制神经细胞PC12的分化。这一研究结果不仅为深入研究LanCL1的功能指明了研究方向，而且还为研究影响神经细胞分化的信号传导通路开启了一个新的研究领域。
该项工作研究期间，美国Oklahoma Medical Research Foundation张凯研究员，Guangpu Li研究员等亦参与了部分研究工作。该研究课题得到了国家自然科学基金委员会、科技部和中国科学院的扶持和资助。（生物谷Bioon.com）
生物谷推荐原始出处：
Genes & Development doi:10.1101/gad.1789209 Genes & Dev. 2009. 23: 1387-1392
Structure of human lanthionine synthetase C-like protein 1 and its interaction with Eps8 and glutathione
Wenchi Zhang1,6, Liang Wang2,6, Yijin Liu1,6, Jiwei Xu1, Guangyu Zhu3, Huaixing Cang1, Xuemei Li1, Mark Bartlam4, Kenneth Hensley5,7, Guangpu Li2, Zihe Rao1,4,8 and Xuejun C. Zhang1,3,9
1National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;
2Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA;
3Protein Studies Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA;
4College of Life Sciences and Tianjin Key Laboratory of Protein Science, Nankai University, Tianjin 300071, China;
5Free Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA
Eukaryotic lanthionine synthetase C-like protein 1 (LanCL1) is homologous to prokaryotic lanthionine cyclases, yet its biochemical functions remain elusive. We report the crystal structures of human LanCL1, both free of and complexed with glutathione, revealing glutathione binding to a zinc ion at the putative active site formed by conserved GxxG motifs. We also demonstrate by in vitro affinity analysis that LanCL1 binds specifically to the SH3 domain of a signaling protein, Eps8. Importantly, expression of LanCL1 mutants defective in Eps8 interaction inhibits nerve growth factor (NGF)-induced neurite outgrowth, providing evidence for the biological significance of this novel interaction in cellular signaling and differentiation.
