The structure and selectivity of the SR protein SRSF2 RRM domain with RNA.
The structure and selectivity of the SR protein SRSF2 RRM domain with RNA.
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DOI：
10.1093/nar/gkr1164
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发表时间：
2012-04
影响因子：
14.9
通讯作者：
Lian LY
中科院分区：
文献类型：
--
作者：
Phelan MM;Goult BT;Clayton JC;Hautbergue GM;Wilson SA;Lian LY
SRSF2是一种典型的SR蛋白，在Pre-mRNA的选择性剪接中发挥重要作用。已证明它参与了维持基因组稳定性的调节途径，并在调节心脏关键受体方面发挥重要作用。我们报道了游离的人SRSF2(残基9-101)的RNA识别基序(RRM)结构域的溶液结构。与SR蛋白家族的其他成员相比，SRSF2结构具有更长的L3环区。RNP2基序中保守的芳香残基在SRSF2中缺失。量热滴定表明，5‘AGCAGAGUA3’序列与SRSF2结合的Kd为61 ± 1 nM，化学计量比为1：1。核磁共振和诱变实验表明，对于SF2，正则的β1和β3相互作用本身并不足以与有效的RNA结合，额外的环L3对于RNA复合体的形成是至关重要的。比较了SRSF2-RNA复合体与其他已知的SR蛋白质RNA复合体的结构。我们得出结论，涉及RRM结构域的L3环、N-和C-末端的相互作用对于决定蛋白质和RNA之间的选择性是共同重要的。
SRSF2 is a prototypical SR protein which plays important roles in the alternative splicing of pre-mRNA. It has been shown to be involved in regulatory pathways for maintaining genomic stability and play important roles in regulating key receptors in the heart. We report here the solution structure of the RNA recognition motifs (RRM) domain of free human SRSF2 (residues 9–101). Compared with other members of the SR protein family, SRSF2 structure has a longer L3 loop region. The conserved aromatic residue in the RNP2 motif is absent in SRSF2. Calorimetric titration shows that the RNA sequence 5′AGCAGAGUA3′ binds SRSF2 with a Kd of 61 ± 1 nM and a 1:1 stoichiometry. NMR and mutagenesis experiments reveal that for SFSF2, the canonical β1 and β3 interactions are themselves not sufficient for effective RNA binding; the additional loop L3 is crucial for RNA complex formation. A comparison is made between the structures of SRSF2–RNA complex with other known RNA complexes of SR proteins. We conclude that interactions involving the L3 loop, N- and C-termini of the RRM domain are collectively important for determining selectivity between the protein and RNA.
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影响因子：
5.6
作者：
Holbrook, JA;Tsodikov, OV;Record, MT
通讯作者：
Record, MT
影响因子：
5.5
作者：
Chandradas, Sajiv;Deikus, Gintaras;Bogdanov, Vladimir Y.
通讯作者：
Bogdanov, Vladimir Y.
影响因子：
2.9
作者：
McLaughlin, Krystle J.;Jenkins, Jermaine L.;Kielkopf, Clara L.
通讯作者：
Kielkopf, Clara L.
影响因子：
4.5
作者：
Cavaloc, Y;Bourgeois, CF;Stévenin, J
通讯作者：
Stévenin, J
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL