6ZPN

Crystal structure of Chaetomium thermophilum Raptor

6ZPN の概要

• エントリーDOI: 10.2210/pdb6zpn/pdb
• 分子名称: WD_REPEATS_REGION domain-containing protein (1 entity in total)
• 機能のキーワード: mtor complex 1, cell growth and metabolism, protein binding
• 由来する生物種: Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 339275.47

構造登録者

Imseng, S.,Boehm, R.,Jakob, R.P.,Hall, M.N.,Hiller, S.,Maier, T. (登録日: 2020-07-08, 公開日: 2021-05-19, 最終更新日: 2024-01-31)

主引用文献

Bohm, R.,Imseng, S.,Jakob, R.P.,Hall, M.N.,Maier, T.,Hiller, S.
The dynamic mechanism of 4E-BP1 recognition and phosphorylation by mTORC1.
Mol.Cell, 81:2403-, 2021

PubMed Abstract: The activation of cap-dependent translation in eukaryotes requires multisite, hierarchical phosphorylation of 4E-BP by the 1 MDa kinase mammalian target of rapamycin complex 1 (mTORC1). To resolve the mechanism of this hierarchical phosphorylation at the atomic level, we monitored by NMR spectroscopy the interaction of intrinsically disordered 4E binding protein isoform 1 (4E-BP1) with the mTORC1 subunit regulatory-associated protein of mTOR (Raptor). The N-terminal RAIP motif and the C-terminal TOR signaling (TOS) motif of 4E-BP1 bind separate sites in Raptor, resulting in avidity-based tethering of 4E-BP1. This tethering orients the flexible central region of 4E-BP1 toward the mTORC1 kinase site for phosphorylation. The structural constraints imposed by the two tethering interactions, combined with phosphorylation-induced conformational switching of 4E-BP1, explain the hierarchy of 4E-BP1 phosphorylation by mTORC1. Furthermore, we demonstrate that mTORC1 recognizes both free and eIF4E-bound 4E-BP1, allowing rapid phosphorylation of the entire 4E-BP1 pool and efficient activation of translation. Finally, our findings provide a mechanistic explanation for the differential rapamycin sensitivity of the 4E-BP1 phosphorylation sites.

PubMed: 33852892
DOI: 10.1016/j.molcel.2021.03.031

実験手法

X-RAY DIFFRACTION (3.5 Å)