3WW0

Crystal structure of F97A mutant, a new nuclear transport receptor of Hsp70

3WW0 の概要

• エントリーDOI: 10.2210/pdb3ww0/pdb
• 関連するPDBエントリー: 3WVZ
• 分子名称: Protein Hikeshi (3 entities in total)
• 機能のキーワード: nuclear transport receptor, transport protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm, cytosol : Q53FT3 Q53FT3
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 43360.24

構造登録者

Song, J.,Kose, S.,Watanabe, A.,Son, S.Y.,Choi, S.,Hong, R.H.,Yamashita, E.,Park, I.Y.,Imamoto, N.,Lee, S.J. (登録日: 2014-06-12, 公開日: 2015-03-25, 最終更新日: 2024-03-20)

主引用文献

Song, J.,Kose, S.,Watanabe, A.,Son, S.Y.,Choi, S.,Hong, H.,Yamashita, E.,Park, I.Y.,Imamoto, N.,Lee, S.J.
Structural and functional analysis of Hikeshi, a new nuclear transport receptor of Hsp70s
Acta Crystallogr.,Sect.D, 71:473-483, 2015

PubMed Abstract: Hikeshi is a nuclear transport receptor required for cell survival after stress. It mediates heat-shock-induced nuclear import of 70 kDa heat-shock proteins (Hsp70s) through interactions with FG-nucleoporins (FG-Nups), which are proteins in nuclear pore complexes (NPCs). Here, the crystal structure of human Hikeshi is presented at 1.8 Å resolution. Hikeshi forms an asymmetric homodimer that is responsible for the interaction with Hsp70s. The asymmetry of Hikeshi arises from the distinct conformation of the C-terminal domain (CTD) and the flexibility of the linker regions of each monomer. Structure-guided mutational analyses showed that both the flexible linker region and the CTD are important for nuclear import of Hsp70. Pull-down assays revealed that only full-length Hsp70s can interact with Hikeshi. The N-terminal domain (NTD) consists of a jelly-roll/β-sandwich fold structure which contains hydrophobic pockets involved in FG-Nup recognition. A unique extended loop (E-loop) in the NTD is likely to regulate the interactions of Hikeshi with FG-Nups. The crystal structure of Hikeshi explains how Hikeshi participates in the regulation of nuclear import through the recognition of FG-Nups and which part of Hikeshi affects its binding to Hsp70. This study is the first to yield structural insight into this highly unique import receptor.

PubMed: 25760597
DOI: 10.1107/S1399004714026881

実験手法

X-RAY DIFFRACTION (2.5 Å)