Modular recognition of RNA by a human pumilio-homology domain
Modular recognition of RNA by a human pumilio-homology domain
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DOI：
10.1016/s0092-8674(02)00873-5
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发表时间：
2002-08-23
期刊：
影响因子：
64.5
通讯作者：
Hall, TMT
中科院分区：
文献类型：
--
作者：
Wang, XQ;McLachlan, J;Hall, TMT
PUF蛋白是一种发育调节剂，通过与其靶mRNAs的3‘非翻译区的序列结合来控制mRNA的稳定性和翻译。我们已经确定了人PUF蛋白的RNA结合域的结构，Pumilio 1与一个高亲和力的RNA配体结合。RNA结合在分子的凹面，在那里蛋白质的八个重复序列中的每一个都通过保守位置的三个氨基酸侧链与不同的RNA碱基接触。我们在一个重复中突变了这三个侧链，从而改变了Pumilio 1的序列特异性。因此，PUM-HD对RNA的高亲和力和特异性是通过使用一个简单重复基序的多个拷贝来实现的。
Puf proteins are developmental regulators that control mRNA stability and translation by binding sequences in the 3' untranslated regions of their target mRNAs. We have determined the structure of the RNA binding domain of the human Puf protein, Pumilio 1 , bound to a high-affinity RNA ligand. The RNA binds the concave surface of the molecule, where each of the protein's eight repeats makes contacts with a different RNA base via three amino acid side chains at conserved positions. We have mutated these three side chains in one repeat, thereby altering the sequence specificity of Pumilio 1. Thus, the high affinity and specificity of the PUM-HD for RNA is achieved using multiple copies of a simple repeated motif.