Deng Lu, Starostina Natalia G, Liu Zhi-Jie, Rose John P, Terns Rebecca M, Terns Michael P, Wang Bi-Cheng
Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA.
Biochem Biophys Res Commun. 2004 Mar 12;315(3):726-32. doi: 10.1016/j.bbrc.2004.01.114.
The methyltransferase fibrillarin is the catalytic component of ribonucleoprotein complexes that direct site-specific methylation of precursor ribosomal RNA and are critical for ribosome biogenesis in eukaryotes and archaea. Here we report the crystal structure of a fibrillarin ortholog from the hyperthermophilic archaeon Pyrococcus furiosus at 1.97A resolution. Comparisons of the X-ray structures of fibrillarin orthologs from Methanococcus jannashii and Archaeoglobus fulgidus reveal nearly identical backbone configurations for the catalytic C-terminal domain with the exception of a unique loop conformation at the S-adenosyl-l-methionine (AdoMet) binding pocket in P. furiosus. In contrast, the N-terminal domains are divergent which may explain why some forms of fibrillarin apparently homodimerize (M. jannashii) while others are monomeric (P. furiosus and A. fulgidus). Three positively charged amino acids surround the AdoMet-binding site and sequence analysis indicates that this is a conserved feature of both eukaryotic and archaeal fibrillarins. We discuss the possibility that these basic residues of fibrillarin are important for RNA-guided rRNA methylation.
甲基转移酶纤维原蛋白是核糖核蛋白复合物的催化成分,可指导前体核糖体RNA的位点特异性甲基化,对真核生物和古细菌中的核糖体生物合成至关重要。在此,我们报告了嗜热古细菌激烈火球菌中纤维原蛋白直系同源物的晶体结构,分辨率为1.97埃。对詹氏甲烷球菌和嗜热栖热菌中纤维原蛋白直系同源物的X射线结构比较显示,催化性C末端结构域的主链构型几乎相同,但激烈火球菌中S-腺苷-L-甲硫氨酸(AdoMet)结合口袋处有独特的环构象除外。相比之下,N末端结构域有所不同,这可能解释了为何某些形式的纤维原蛋白明显形成同二聚体(詹氏甲烷球菌),而其他形式则为单体(激烈火球菌和嗜热栖热菌)。三个带正电荷的氨基酸围绕着AdoMet结合位点,序列分析表明这是真核和古细菌纤维原蛋白的保守特征。我们讨论了纤维原蛋白的这些碱性残基对RNA引导的rRNA甲基化很重要的可能性。