A) 人源LanCL1三維結(jié)構(gòu)的主鏈飄帶示意圖. 外圍螺旋和內(nèi)層螺旋分別顯示紅色和黃色. (B) 人源LanCL1的表面電勢(shì)圖. 球棍模型表示結(jié)合的谷胱甘肽. (C) 顯示經(jīng)過空pBI/eGFP vector或LanCL1野生型或各種突變體轉(zhuǎn)染的PC12細(xì)胞用50 ng/ml NGF處理后四天的熒光顯微圖片.
近期,，著名期刊《基因與發(fā)育》（Genes & Development）發(fā)表了中科院院士饒子和領(lǐng)導(dǎo)的中國科學(xué)院生物物理所/清華大學(xué)/南開大學(xué)聯(lián)合實(shí)驗(yàn)室在人源LanCL1 (lanthionine synthetase C-like protein-1)蛋白研究上的最新研究成果,，論文題為Structure of Human Lanthionine Synthetase C-like Protein 1 and Its Interaction with Eps8 and Glutathione,。
人源LanCL1是一類功能研究較少的蛋白，與原核生物L(fēng)anC (lanthionine cyclase）在序列上只有約15%的同源性,。該實(shí)驗(yàn)室得到了人源LanCL1以及其與谷胱甘肽復(fù)合物的三維晶體結(jié)構(gòu),。通過對(duì)該結(jié)構(gòu)的分析，他們發(fā)現(xiàn)該蛋白有可能是一個(gè)能直接耦合細(xì)胞氧化還原狀態(tài)與生長因子受體通路信號(hào)轉(zhuǎn)導(dǎo)的分子,。進(jìn)一步的突變實(shí)驗(yàn)和體外SPR(表面等離子體共振技術(shù))等實(shí)驗(yàn)證實(shí)人源LanCL1能特異性地結(jié)合生長因子信號(hào)傳導(dǎo)相關(guān)的蛋白EPS8（生長因子受體底物蛋白8）上 的SH3 domain,，并且這一相互作用受谷胱甘肽的調(diào)節(jié)。在此基礎(chǔ)上,，細(xì)胞實(shí)驗(yàn)也表明所有能減弱與EPS8相互作用的突變體均能抑制神經(jīng)細(xì)胞PC12的分化,。這一研究結(jié)果不僅為深入研究LanCL1的功能指明了研究方向，而且還為研究影響神經(jīng)細(xì)胞分化的信號(hào)傳導(dǎo)通路開啟了一個(gè)新的研究領(lǐng)域,。
該項(xiàng)工作研究期間,，美國Oklahoma Medical Research Foundation張凱研究員，Guangpu Li研究員等亦參與了部分研究工作,。該研究課題得到了國家自然科學(xué)基金委員會(huì),、科技部和中國科學(xué)院的扶持和資助。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
