3UVU

Structural basis of nuclear import of Flap endonuclease 1 (FEN1)

3UVU の概要

• エントリーDOI: 10.2210/pdb3uvu/pdb
• 関連するPDBエントリー: 1PJM 1PJN 3RZ9 3RZX
• 分子名称: Flap endonuclease 1 (Fen1) peptide, Importin subunit alpha-2 (3 entities in total)
• 機能のキーワード: fen 1, flap endonuclease 1, protein binding-peptide complex, protein binding/peptide
• 由来する生物種: Mus musculus (mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 57438.06

構造登録者

Barros, A.C.,Takeda, A.A.S.,Fontes, M.R.M. (登録日: 2011-11-30, 公開日: 2012-06-27, 最終更新日: 2024-02-28)

主引用文献

de Barros, A.C.,Takeda, A.A.,Chang, C.W.,Kobe, B.,Fontes, M.R.
Structural basis of nuclear import of flap endonuclease 1 (FEN1).
Acta Crystallogr.,Sect.D, 68:743-750, 2012

PubMed Abstract: 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 α, the crystal structure of the complex of importin α 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 (354)KRKX(8)KKK(367) sequence, it is the (354)KRX(10)KKAK(369) sequence that binds to importin α. This result explains the incomplete inhibition of localization that was observed on mutating residues (365)KKK(367). Acidic and polar residues in the X(10) linker region close to the basic clusters play an important role in binding to importin α. 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.

PubMed: 22751659
DOI: 10.1107/S0907444912010281

実験手法

X-RAY DIFFRACTION (2.38 Å)