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首页> 外文期刊>Acta crystallographica.Section D. Biological crystallography >Structural basis of nuclear import of flap endonuclease 1 (FEN1)
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Structural basis of nuclear import of flap endonuclease 1 (FEN1)

机译:核进口挡板的结构基础核酸内切酶1 (FEN1)

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Flap endonuclease 1 (FEN1) is a member of the nuclease family and is structurally conserved from bacteriophages to humans. This protein is involved in multiple DNA-processing pathways, including Okazaki fragment maturation, stalled replication-fork rescue, telomere maintenance, long-patch base-excision repair and apoptotic DNA fragmentation. FEN1 has three functional motifs that are responsible for its nuclease, PCNA-interaction and nuclear localization activities, respectively. It has been shown that the C-terminal nuclear localization sequence (NLS) facilitates nuclear localization of the enzyme during the S phase of the cell cycle and in response to DNA damage. To determine the structural basis of the recognition of FEN1 by the nuclear import receptor importin , the crystal structure of the complex of importin with a peptide corresponding to the FEN1 NLS was solved. Structural studies confirmed the binding of the FEN1 NLS as a classical bipartite NLS; however, in contrast to the previously proposed 354KRKX 8KKK 367 sequence, it is the 354KRX 10KKAK 369 sequence that binds to importin . This result explains the incomplete inhibition of localization that was observed on mutating residues 365KKK 367. Acidic and polar residues in the X 10 linker region close to the basic clusters play an important role in binding to importin . These results suggest that the basic residues in the N-terminal basic cluster of bipartite NLSs may play roles that are more critical than those of the many basic residues in the C - terminal basic cluster.
机译:皮瓣核酸内切酶1 (FEN1)的一员核酸酶家族和结构守恒的人类从噬菌体。参与多个dna的加工途径方面取得,包括冈崎片段成熟,停滞不前复制叉救援,端粒的维护,long-patch base-excision DNA修复和凋亡碎片。负责它的核酸酶,PCNA-interaction和核本地化分别活动。c端核本地化序列(NLS)促进核本地化酶在S期的细胞周期为了应对DNA损伤。结构性FEN1的识别的基础核进口受体importin,复杂的输入蛋白α的晶体结构肽FEN1 NLS对应解决了。FEN1 NLS的经典一式两份的NLS;然而,相比以前提出354 krkx 8三k党367年序列,是354年的期货交易所369 kkak importin结合序列。结果解释不完全抑制本地化是观察到的变异残留365三k党367。X 10链接器区域基本接近集群中扮演重要角色绑定importin。残留的氨基端基本集群一式两份的nls可能扮演角色比许多基本残留的关键C -末端基本集群。

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