Leulliot Nicolas, Godin Katherine S, Hoareau-Aveilla Coralie, Quevillon-Cheruel Sophie, Varani Gabriele, Henry Yves, Van Tilbeurgh Herman
Institut de Biochimie et de Biophysique Moléculaire et Cellulaire, UMR8619, Bât 430, Université de Paris-Sud, 91405 Orsay Cedex, France.
J Mol Biol. 2007 Aug 31;371(5):1338-53. doi: 10.1016/j.jmb.2007.06.031. Epub 2007 Jun 16.
Naf1 is an essential protein involved in the maturation of box H/ACA ribonucleoproteins, a group of particles required for ribosome biogenesis, modification of spliceosomal small nuclear RNAs and telomere synthesis. Naf1 participates in the assembly of the RNP at transcription sites and in the nuclear trafficking of the complex. The crystal structure of a domain of yeast Naf1p, Naf1Delta1p, reveals a striking structural homology with the core domain of archaeal Gar1, an essential protein component of the mature RNP; it suggests that Naf1p and Gar1p have a common binding site on the enzymatic protein component of the particle, Cbf5p. We propose that Naf1p is a competitive binder for Cbf5p, which is replaced by Gar1p during maturation of the H/ACA particle. The exchange of Naf1p by Gar1p might be prompted by external factors that alter the oligomerisation state of Naf1p and Gar1p. The structural homology with Gar1 suggests that the function of Naf1 involves preventing non-cognate RNAs from being loaded during transport of the particle by inducing a non-productive conformation of Cbf5.
Naf1是一种参与盒式H/ACA核糖核蛋白成熟过程的必需蛋白，盒式H/ACA核糖核蛋白是核糖体生物合成、剪接体小核RNA修饰和端粒合成所需的一组颗粒。Naf1参与RNP在转录位点的组装以及该复合物在细胞核内的运输。酵母Naf1p的一个结构域Naf1Delta1p的晶体结构显示，它与古细菌Gar1的核心结构域具有显著的结构同源性，Gar1是成熟RNP的一种必需蛋白质成分；这表明Naf1p和Gar1p在颗粒的酶蛋白成分Cbf5p上有一个共同的结合位点。我们提出，Naf1p是Cbf5p的竞争性结合剂，在H/ACA颗粒成熟过程中被Gar1p取代。Naf1p被Gar1p取代可能是由改变Naf1p和Gar1p寡聚化状态的外部因素所引发。与Gar1的结构同源性表明，Naf1的功能包括通过诱导Cbf5的非生产性构象来防止在颗粒运输过程中加载非同源RNA。
