Structural basis for the specificity of bipartite nuclear localization sequence binding by importin-α
Structural basis for the specificity of bipartite nuclear localization sequence binding by importin-α
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DOI：
10.1074/jbc.m303275200
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发表时间：
2003-07-25
影响因子：
4.8
通讯作者：
Kobe, B
中科院分区：
文献类型：
--
作者：
Fontes, MRM;Teh, T;Kobe, B
Importin-α是核输入受体，其识别携带常规的基本单组分和双组分核定位序列（NLS）的货物蛋白，并促进它们转运到核中。二分NLS含有两簇碱性残基，通过可变长度的接头连接。要确定的结构基础的识别多样的二分NLS的哺乳动物importin-alpha，我们共结晶的非自抑制小鼠受体蛋白与肽对应的NLS从人视网膜母细胞瘤蛋白和非洲爪蟾磷蛋白N1 N2，含有不同的序列和长度的接头。我们发现，基本的集群相互作用类似于在两个NLS，但接头序列采用不同的构象，而两者都使特定的接触与受体。现有的数据使我们能够得出一般性的结论，NLS结合的特异性importin-alpha和促进传统的基本/二分NLS（KRX 10 - 12 KRRK），可用于识别新的核蛋白的共识序列的改进定义。
Importin-alpha is the nuclear import receptor that recognizes cargo proteins carrying conventional basic monopartite and bipartite nuclear localization sequences (NLSs) and facilitates their transport into the nucleus. Bipartite NLSs contain two clusters of basic residues, connected by linkers of variable lengths. To determine the structural basis of the recognition of diverse bipartite NLSs by mammalian importin-alpha, we co-crystallized a non-autoinhibited mouse receptor protein with peptides corresponding to the NLSs from human retinoblastoma protein and Xenopus laevis phosphoprotein N1N2, containing diverse sequences and lengths of the linker. We show that the basic clusters interact analogously in both NLSs, but the linker sequences adopt different conformations, whereas both make specific contacts with the receptor. The available data allow us to draw general conclusions about the specificity of NLS binding by importin-alpha and facilitate an improved definition of the consensus sequence of a conventional basic/bipartite NLS (KRX10-12KRRK) that can be used to identify novel nuclear proteins.