3EBM

Crystal structure of human translationally controlled tumour associated protein (hTCTP) mutant E12V

3EBM の概要

• エントリーDOI: 10.2210/pdb3ebm/pdb
• 関連するPDBエントリー: 1YZ1
• 分子名称: Translationally-controlled tumor protein (2 entities in total)
• 機能のキーワード: tctp, e12v, calcium, cytoplasm, phosphoprotein, calcium-binding protein
• 由来する生物種: Homo sapiens (man)
• 細胞内の位置: Cytoplasm: P13693
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 82642.06

構造登録者

Yang, B.,Dong, X.,Zhong, C.,Ding, J. (登録日: 2008-08-28, 公開日: 2009-06-30, 最終更新日: 2024-10-30)

主引用文献

Dong, X.,Yang, B.,Li, Y.,Zhong, C.,Ding, J.
Molecular basis of the acceleration of the GDP-GTP exchange of human ras homolog enriched in brain by human translationally controlled tumor protein.
J.Biol.Chem., 284:23754-23764, 2009

PubMed Abstract: Ras homolog enriched in brain (Rheb), a small GTPase, positively regulates the mTORC1 pathway. The GDP-GTP exchange of Rheb has been suggested to be facilitated by translationally controlled tumor protein (TCTP). Here we demonstrate that human TCTP (hTCTP) interacts with human Rheb (hRheb) and accelerates its GDP release in vitro and that hTCTP activates the mTORC1 pathway in vivo. To investigate the underlying mechanism, we built structure models of GDP- and GTP-bound hRheb in complexes with hTCTP and performed molecular dynamics simulations of the models, which predict key residues involved in the interactions and region of hRheb undergoing conformational change during the GDP-GTP exchange. These results are verified with site-directed mutagenesis and in vitro biochemical and in vivo cell biological analyses. Furthermore, a crystal structure of the E12V mutant hTCTP, which lacks the guanine nucleotide exchange factor activity, shows that the deficiency appears to be caused by loss of a salt-bridging interaction with Lys-45 of hRheb. These data collectively provide insights into the molecular mechanisms of how hTCTP interacts with hRheb and activates the mTORC1 pathway.

PubMed: 19570981
DOI: 10.1074/jbc.M109.012823

実験手法

X-RAY DIFFRACTION (2.6 Å)