Structural basis for recruitment of human flap endonuclease 1 to PCNA
Structural basis for recruitment of human flap endonuclease 1 to PCNA
复制标题
DOI：
10.1038/sj.emboj.7600519
复制
发表时间：
2005-02-23
期刊：
影响因子：
11.4
通讯作者：
Hakoshima, T
中科院分区：
文献类型：
--
作者：
Sakurai, S;Kitano, K;Hakoshima, T
皮瓣核酸内切酶-1（FEN 1）是维持基因组稳定性和复制的关键酶。增殖细胞核抗原（PCNA）结合FEN 1并刺激其核酸内切酶活性。人FEN 1和PCNA之间的复合物的晶体结构揭示了FEN 1与PCNA相互作用的结构基础。主要界面涉及FEN 1的C-末端尾，其形成通过短螺旋连接的两条β-链，即β A-α A-β B基序，参与与PCNA的β-β和疏水相互作用。这些相互作用类似于先前对p21（CIP 1/WAF 1）肽观察到的那些。然而，这种涉及全长酶的结构揭示了涉及核心结构域的额外界面。界面处的相互作用使酶保持在无活性的“锁定”方向，并且可能通过保留PCNA的中心孔用于沿DNA沿着而用于快速DNA追踪。存在于FEN 1的核心结构域和C-末端尾部之间的铰链区将在将FEN 1取向从无活性取向转换为活性取向中起作用。
Flap endonuclease- 1 ( FEN1) is a key enzyme for maintaining genomic stability and replication. Proliferating cell nuclear antigen ( PCNA) binds FEN1 and stimulates its endonuclease activity. The structural basis of the FEN1 PCNA interaction was revealed by the crystal structure of the complex between human FEN1 and PCNA. The main interface involves the C- terminal tail of FEN1, which forms two beta- strands connected by a short helix, the betaA -alphaA -betaB motif, participating in beta-beta and hydrophobic interactions with PCNA. These interactions are similar to those previously observed for the p21(CIP1/ WAF1) peptide. However, this structure involving the full- length enzyme has revealed additional interfaces that are involved in the core domain. The interactions at the interfaces maintain the enzyme in an inactive ' locked- down' orientation and might be utilized in rapid DNA- tracking by preserving the central hole of PCNA for sliding along the DNA. A hinge region present between the core domain and the C- terminal tail of FEN1 would play a role in switching the FEN1 orientation from an inactive to an active orientation.