Structural basis of the interaction between P-element somatic inhibitor and U1-70k essential for the alternative splicing of P-element transposase
Structural basis of the interaction between P-element somatic inhibitor and U1-70k essential for the alternative splicing of P-element transposase
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DOI：
10.1016/j.jmb.2005.04.077
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发表时间：
2005-08-05
影响因子：
5.6
通讯作者：
Nagai, K
中科院分区：
文献类型：
--
作者：
Ignjatovic, T;Yang, JC;Nagai, K
果蝇中P元件转座受P元件转座酶前体mRNA的组织特异性选择性剪接调控。在体细胞中，P-元件体细胞抑制剂（PSI）蛋白与前体mRNA的外显子3结合，并将U1小核核糖核蛋白（snRNP）募集到F1假剪接位点。这消除了U1 snRNP与真正的5'剪接位点的结合，从而防止了第三内含子的切除。两个同源短序列，称为A和B盒，靠近PSI的C末端结合到U1 snRNP内的U1- 70 k蛋白。我们现在已经将U1- 70 k的AB盒结合位点映射到C末端的一个短的富含脯氨酸的序列。我们的核磁共振研究表明，B盒形成一个反平行的螺旋发夹，其中四个高度保守的芳香族残基在第一个螺旋的一面上形成一个簇。该疏水簇与U1- 70 k蛋白的富含脯氨酸的区域广泛相互作用。(c)2005爱思唯尔有限公司保留所有权利。
P-element transposition in Drosophila is regulated by tissue-specific alternative splicing of the P-element transposase pre-mRNA. In somatic cells, the P-element somatic inhibitor (PSI) protein binds to exon 3 of the pre-mRNA and recruits U1 small nuclear ribonucleoprotein (snRNP) to the F1 pseudo-splice site. This abrogates binding of U1 snRNP to the genuine 5' splice site, thereby preventing excision of the third intron. Two homologous short sequences, referred to as the A and B boxes, near the C terminus of PSI bind to U1-70k protein within U1 snRNP. We have now mapped the AB box-binding site of U1-70k to a short proline-rich sequence at the C terminus. Our NMR study shows that the B box forms an anti-parallel helical hairpin in which four highly conserved aromatic residues form a cluster on one face of the first helix. This hydrophobic cluster interacts extensively with the proline-rich region of the U1-70k protein. (c) 2005 Elsevier Ltd. All rights reserved.