The Ighmbp2 helicase structure reveals the molecular basis for disease-causing mutations in DMSA1.
The Ighmbp2 helicase structure reveals the molecular basis for disease-causing mutations in DMSA1.
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DOI：
10.1093/nar/gks792
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发表时间：
2012-11
影响因子：
14.9
通讯作者：
Song H
中科院分区：
文献类型：
--
作者：
Lim SC;Bowler MW;Lai TF;Song H
免疫球蛋白微结合蛋白2 （Ighmbp2）突变导致远端脊髓性肌萎缩1型（DSMA1），这是一种常染色体隐性遗传病，临床特征为远端肢体无力和呼吸窘迫。然而，尽管进行了广泛的研究，致病突变的机制仍然难以捉摸。在这里，我们报道了有和没有结合RNA的Ighmbp2解旋酶核心的晶体结构。这些结构表明，Ighmbp2的整体折叠与Upf1非常相似，Upf1是参与无义介导的mRNA衰变的关键解旋酶。与Upf1类似，Ighmbp2结构域1B和1C在RNA结合时也会发生较大的构象变化，分别旋转30°和10°。位于解旋酶核心下游的R3H结构域进一步增强了Ighmbp2的RNA结合和atp酶活性。将DSMA1的致病突变定位到解旋酶核心结构上，为理解Ighmbp2突变的致病后果提供了分子基础。
Mutations in immunoglobulin µ-binding protein 2 (Ighmbp2) cause distal spinal muscular atrophy type 1 (DSMA1), an autosomal recessive disease that is clinically characterized by distal limb weakness and respiratory distress. However, despite extensive studies, the mechanism of disease-causing mutations remains elusive. Here we report the crystal structures of the Ighmbp2 helicase core with and without bound RNA. The structures show that the overall fold of Ighmbp2 is very similar to that of Upf1, a key helicase involved in nonsense-mediated mRNA decay. Similar to Upf1, domains 1B and 1C of Ighmbp2 undergo large conformational changes in response to RNA binding, rotating 30° and 10°, respectively. The RNA binding and ATPase activities of Ighmbp2 are further enhanced by the R3H domain, located just downstream of the helicase core. Mapping of the pathogenic mutations of DSMA1 onto the helicase core structure provides a molecular basis for understanding the disease-causing consequences of Ighmbp2 mutations.
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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
影响因子：
3.5
作者：
de Planell-Saguer, Mariangels;Schroeder, David G.;Mourelatos, Zissimos
通讯作者：
Mourelatos, Zissimos
影响因子：
4.5
作者：
Bhattacharya, A;Czaplinski, K;Peltz, SW
通讯作者：
Peltz, SW
影响因子：
6.1
作者：
Chen, Ying-Zhang;Hashemi, Sayed H.;Bennett, Craig L.
通讯作者：
Bennett, Craig L.
DOI：
10.1107/s0108767311004831
发表时间：
2011-05
期刊：
Acta crystallographica. Section A, Foundations of crystallography
影响因子：
--
作者：
Brockhauser S;White KI;McCarthy AA;Ravelli RB
通讯作者：
Ravelli RB