Structural basis for snRNA recognition by the double-WD40 repeat domain of Gemin5.
Structural basis for snRNA recognition by the double-WD40 repeat domain of Gemin5.
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Gemin5 的双 WD40 重复结构域识别 snRNA 的结构基础。
DOI：
10.1101/gad.291377.116
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发表时间：
2016-11-01
影响因子：
10.5
通讯作者：
Xu RM
中科院分区：
文献类型：
--
作者：
Jin W;Wang Y;Liu CP;Yang N;Jin M;Cong Y;Wang M;Xu RM
在这里，Jin等人确定了Gemin 5与13-nt U4 snRNA oligo复合的晶体结构。Gemin 5是snRNP生物发生所必需的，并与snRNA识别有关。他们的发现为Gemin 5的snRNA结合特异性和WD 40重复蛋白结合RNA的分子机制提供了新的机制见解。剪接体小核核糖核颗粒（snRNP）核心的组装需要多亚基SMN（运动神经元存活）复合物的参与，该复合物包含SMN和几种Gemin蛋白。SMN和Gemin 2亚基直接结合Sm蛋白，Gemin 5是snRNP生物合成所需的，并与snRNA识别有关。snRNP装配所需的RNA序列包括Sm位点和相邻的3′茎环，但缺乏对Gemin 5 RNA结合特异性的精确理解。在这里，我们表明，N-末端的一半Gemin 5，这是由两个并列的七叶WD 40重复结构域，识别Sm网站。串联的WD 40重复结构域刚性地保持在一起以形成连续的RNA结合表面。RNA接触残基主要位于WD 40结构域顶端表面上的β链之间的环上。结构和生化分析表明，涉及四个芳香族残基和氢键的碱基堆积的相互作用，由一对peptides的Sm序列的特异性识别是至关重要的。我们还表明，一个腺嘌呤立即5′的Sm网站是需要有效的结合，Gemin 5可以结合短RNA寡核苷酸在一个替代模式。我们的研究结果提供了机制的理解Gemin 5的snRNA结合特异性，以及有价值的见解的分子机制的RNA结合WD 40重复蛋白一般。
Here, Jin et al. determined the crystal structure of Gemin5 in complex with a 13-nt U4 snRNA oligo. Gemin5 is required for snRNP biogenesis and has been implicated in snRNA recognition. Their findings provide novel mechanistic insights into Gemin5's snRNA-binding specificity and the molecular mechanism of RNA binding by WD40 repeat proteins. Assembly of the spliceosomal small nuclear ribonucleoparticle (snRNP) core requires the participation of the multisubunit SMN (survival of motor neuron) complex, which contains SMN and several Gemin proteins. The SMN and Gemin2 subunits directly bind Sm proteins, and Gemin5 is required for snRNP biogenesis and has been implicated in snRNA recognition. The RNA sequence required for snRNP assembly includes the Sm site and an adjacent 3′ stem–loop, but a precise understanding of Gemin5's RNA-binding specificity is lacking. Here we show that the N-terminal half of Gemin5, which is composed of two juxtaposed seven-bladed WD40 repeat domains, recognizes the Sm site. The tandem WD40 repeat domains are rigidly held together to form a contiguous RNA-binding surface. RNA-contacting residues are located mostly on loops between β strands on the apical surface of the WD40 domains. Structural and biochemical analyses show that base-stacking interactions involving four aromatic residues and hydrogen bonding by a pair of arginines are crucial for specific recognition of the Sm sequence. We also show that an adenine immediately 5′ to the Sm site is required for efficient binding and that Gemin5 can bind short RNA oligos in an alternative mode. Our results provide mechanistic understandings of Gemin5's snRNA-binding specificity as well as valuable insights into the molecular mechanism of RNA binding by WD40 repeat proteins in general.
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影响因子：
10.5
作者：
Chan SL;Huppertz I;Yao C;Weng L;Moresco JJ;Yates JR 3rd;Ule J;Manley JL;Shi Y
通讯作者：
Shi Y
SM级核糖核蛋白的生物发生需要两个不同的精氨酸甲基转移酶。
影响因子：
7.8
作者：
Gonsalvez, Graydon B.;Tian, Liping;Ospina, Jason K.;Boisvert, Francois-Michel;Lamond, Angus I.;Matera, A. Gregory
通讯作者：
Matera, A. Gregory
影响因子：
11.4
作者：
Achsel, T;Brahms, H;Lührmann, R
通讯作者：
Lührmann, R
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH