Structural basis for the activation of the C. elegans noncanonical cytoplasmic poly(A)-polymerase GLD-2 by GLD-3
Structural basis for the activation of the C. elegans noncanonical cytoplasmic poly(A)-polymerase GLD-2 by GLD-3
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GLD-3 激活线虫非经典细胞质聚 (A)-聚合酶 GLD-2 的结构基础
DOI：
10.1073/pnas.1504648112
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Eckmann
中科院分区：
文献类型：
--
作者：
Bonneau;Eckmann
线虫胚系发育缺陷（GLD）-2-GLD-3复合体上调减数分裂进程所需基因的表达。GLD-2-GLD-3通过延长生殖系特异性mRNA的短poly（A）尾，将它们从休眠状态转换为免疫活性状态来发挥作用。GLD-2是一种细胞质非典型的多聚腺苷酸聚合酶，它缺乏典型的核多聚腺苷酸聚合酶Pap 1的RNA结合结构域。C. elegansGLD-2在体内和体外的作用依赖于它与含有多K同源（KH）结构域的蛋白质GLD-3（Bicaudal-C的同源物）的结合。我们已经确定了一个最小的多聚腺苷酸化复合物，其中包括保守的核苷酸转移酶的核心GLD-2和GLD-3的N-末端结构域，并确定其结构在2.3倍分辨率。该结构显示GLD-3的N-末端结构域不折叠到预测的KH结构域中，而是包裹GLD-2的催化结构域。从结构和生物化学数据中出现的图像是，GLD-3通过稳定酶间接激活GLD-2，并直接通过在RNA结合裂缝附近提供带正电荷的残基来激活GLD-2。与聚腺苷酸聚合酶Pap 1和Trf 4相比，GLD-2的RNA结合裂缝具有独特的结构特征。因此，GLD-2具有独特的生物化学特性：它在体外对3′端至少有一个腺苷的单链RNA显示出不寻常的特异性。因此，GLD-2似乎已经进化出与休眠细胞质mRNA的3′端特征相匹配的专门的核苷酸转移酶特性。
TheCaenorhabditis elegansgerm-line development defective (GLD)-2–GLD-3 complex up-regulates the expression of genes required for meiotic progression. GLD-2–GLD-3 acts by extending the short poly(A) tail of germ-line–specific mRNAs, switching them from a dormant state into a translationally active state. GLD-2 is a cytoplasmic noncanonical poly(A) polymerase that lacks the RNA-binding domain typical of the canonical nuclear poly(A)-polymerase Pap1. The activity ofC. elegansGLD-2 in vivo and in vitro depends on its association with the multi-K homology (KH) domain-containing protein, GLD-3, a homolog of Bicaudal-C. We have identified a minimal polyadenylation complex that includes the conserved nucleotidyl-transferase core of GLD-2 and the N-terminal domain of GLD-3, and determined its structure at 2.3-Å resolution. The structure shows that the N-terminal domain of GLD-3 does not fold into the predicted KH domain but wraps around the catalytic domain of GLD-2. The picture that emerges from the structural and biochemical data are that GLD-3 activates GLD-2 both indirectly by stabilizing the enzyme and directly by contributing positively charged residues near the RNA-binding cleft. The RNA-binding cleft of GLD-2 has distinct structural features compared with the poly(A)-polymerases Pap1 and Trf4. Consistently, GLD-2 has distinct biochemical properties: It displays unusual specificity in vitro for single-stranded RNAs with at least one adenosine at the 3′ end. GLD-2 thus appears to have evolved specialized nucleotidyl-transferase properties that match the 3′ end features of dormant cytoplasmic mRNAs.
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脊椎动物种系和大脑中的 GLD2 Poly(A) 聚合酶。
DOI：
10.1261/rna.2630205
发表时间：
2005
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Rouhana,Labib;Wang,Liaoteng;Buter,Natascha;Kwak,JaeEun;Schiltz,CraigA;Gonzalez,Tania;Kelley,AnnE;Landry,CharlesF;Wickens,Marvin
通讯作者：
Wickens,Marvin
影响因子：
16
作者：
Udagawa, Tsuyoshi;Swanger, Sharon A.;Takeuchi, Koichi;Kim, Jong Heon;Nalavadi, Vijayalaxmi;Shin, Jihae;Lorenz, Lori J.;Zukin, R. Suzanne;Bassell, Gary J.;Richter, Joel D.
通讯作者：
Richter, Joel D.
DOI：
10.1073/pnas.1003505107
发表时间：
2010-08-24
影响因子：
11.1
作者：
Hamill, Stephanie;Wolin, Sandra L.;Reinisch, Karin M.
通讯作者：
Reinisch, Karin M.
DOI：
10.1016/j.bbagrm.2007.12.003
发表时间：
2008-04
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
G. Martin;S. Doublié;W. Keller
通讯作者：
G. Martin;S. Doublié;W. Keller
影响因子：
11.8
作者：
Eckmann, CR;Kraemer, B;Kimble, J
通讯作者：
Kimble, J