細(xì)胞》子刊《結(jié)構(gòu)》（Structure）雜志于4月15日發(fā)表了中國(guó)科學(xué)院上海生命科學(xué)研究院生物化學(xué)與細(xì)胞生物學(xué)研究所丁建平研究員課題組的一項(xiàng)新研究成果,，該項(xiàng)工作發(fā)現(xiàn)了小G蛋白與效應(yīng)蛋白相互作用的一種新方式,。
小G蛋白家族成員在信號(hào)通路中發(fā)揮分子開關(guān)的功能，參與調(diào)控很多生物學(xué)過(guò)程。當(dāng)小G蛋白結(jié)合GTP時(shí)處于活性狀態(tài),、結(jié)合GDP時(shí)處于非活性狀態(tài),。小G蛋白激活后一般通過(guò)開關(guān)（Switch）區(qū)域與效應(yīng)蛋白結(jié)合,，從而調(diào)控下游信號(hào)通路,。小G蛋白ARL家族成員ARL2參與細(xì)胞內(nèi)微管組裝的調(diào)控。此外,，ARL2通過(guò)與效應(yīng)蛋白BART的結(jié)合,，維持 STAT3在細(xì)胞核內(nèi)的定位，并參與線粒體ATP/ADP通道的調(diào)控,。丁建平課題組博士生張?zhí)忑埖冗\(yùn)用結(jié)構(gòu)生物學(xué)的方法解析了ARL2-GTP-BART復(fù)合物的晶體結(jié)構(gòu),，發(fā)現(xiàn)ARL2以一種新的方式識(shí)別和結(jié)合BART，并進(jìn)一步運(yùn)用生物化學(xué)和分子生物學(xué)方法對(duì)ARL2-BART之間的相互作用進(jìn)行了驗(yàn)證,。目前發(fā)現(xiàn)的ARL家族其他成員通過(guò)開關(guān)區(qū)域與效應(yīng)蛋白相互作用,，其N端α螺旋通過(guò)脂酰修飾定位在高爾基體膜上、不參與效應(yīng)蛋白的結(jié)合,。而ARL2除了通過(guò)其開關(guān)區(qū)域識(shí)別BART外,，還利用N端α螺旋識(shí)別和結(jié)合BART表面的一疏水口袋,，以增強(qiáng)對(duì)效應(yīng)蛋白的特異性識(shí)別和結(jié)合,、從而精確調(diào)控下游信號(hào)通路。這種作用方式在小G蛋白與效應(yīng)蛋白相互作用研究中是首次被發(fā)現(xiàn),。這一研究成果對(duì)進(jìn)一步研究ARL家族成員的結(jié)構(gòu)與功能的關(guān)系,，闡釋ARL家族成員之間、以及與其它小G蛋白的功能差異的分子基礎(chǔ)具有重要意義,。
該項(xiàng)工作得到國(guó)家科技部,、國(guó)家自然科學(xué)基金、中國(guó)科學(xué)院和上海市科委的經(jīng)費(fèi)支持,。（生物谷Bioon.com）
生物谷推薦原始出處：
Structure,，doi:10.1016/j.str.2009.01.014，Tianlong Zhang,，Jianping Ding
Crystal Structure of the ARL2-GTP-BART Complex Reveals a Novel Recognition and Binding Mode of Small GTPase with Effector
Tianlong Zhang1,2,Sheng Li1,2,Yichen Zhang1,Chen Zhong1,Zheng Lai1andJianping Ding1,,
1 State Key Laboratory of Molecular Biology and Research Center for Structural Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences
2 Graduate School of the Chinese Academy of Sciences Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China
ARL2 is a member of the ADP-ribosylation factor family but has unique biochemical features. BART is an effector of ARL2 that is essential for nuclear retention of STAT3 and may also be involved in mitochondria transport and apoptosis. Here we report the crystal structure and biochemical characterization ofhuman ARL2-GTP-BART complex. ARL2-GTP assumes a typical small GTPase fold with a unique N-terminal α helix conformation. BART consists of a six α helix bundle. The interactions between ARL2 and BART involve two interfaces: a conserved N-terminal LLXIL motif of ARL2 is embedded in a hydrophobic cleft of BART and the switch regions of ARL2 interact with helix α3 of BART. Both interfaces are essential for the binding as verified by mutagenesis study. This novel recognition and binding mode is different from that of other small GTPase-effector interactions and provides molecular basis for the high specificity of ARL2 for BART.
