X-ray crystallographic and NMR studies of the third KH domain of hnRNP K in complex with single-stranded nucleic acids
X-ray crystallographic and NMR studies of the third KH domain of hnRNP K in complex with single-stranded nucleic acids
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DOI：
10.1016/j.str.2005.04.008
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发表时间：
2005-07-01
期刊：
影响因子：
5.7
通讯作者：
Cusack, S
中科院分区：
文献类型：
--
作者：
Backe, PH;Messias, AC;Cusack, S
异质核核糖核蛋白（hnRNP）K参与基因表达调控的多种功能，并在涉及核酸的信号传导途径和过程的交叉点处充当枢纽。其功能的核心是其通过其KH（hnRNP K同源性）结构域结合ssDNA和ssRNA的能力。我们确定的晶体结构的hnRNP K KH 3结构域与15聚体和6聚体（CTC 4）的ssDNA复合在2.4和1.8埃分辨率，分别，并显示KH 3结构域结合特异性的TCCC和CCCC序列。同时，我们使用NMR来比较KH 3结构域与几种ssRNA配体和CTC 4 ssDNA的结合亲和力和相互作用模式。基于KH 3-CTC 4复合物与其他KH结构域与ssRNA复合物的已知结构的结构比对，我们讨论了KH结构域对四核苷酸序列的识别。
The heterogeneous nuclear ribonucleoprotein (hnRNP) K is implicated in multiple functions in the regulation of gene expression and acts as a hub at the intersection of signaling pathways and processes involving nucleic acids. Central to its function is its ability to bind both ssDNA and ssRNA via its KH (hnRNP K homology) domains. We determined crystal structures of hnRNP K KH3 domain complexed with 15-mer and 6-mer (CTC4) ssDNAs at 2.4 and 1.8 angstrom resolution, respectively, and show that the KH3 domain binds specifically to both TCCC and CCCC sequences. In parallel, we used NMR to compare the binding affinity and mode of interaction of the KH3 domain with several ssRNA ligands and CTC4 ssDNA. Based on a structure alignment of the KH3-CTC4 complex with known structures of other KH domains in complex with ssRNA, we discuss recognition of tetranucleotide sequences by KH domains.