9F43

cryo-EM structure of human LST2 bound to human mTOR complex 1, focused on RAPTOR

9F43 の概要

• エントリーDOI: 10.2210/pdb9f43/pdb
• EMDBエントリー: 50182
• 分子名称: Regulatory-associated protein of mTOR, Lateral signaling target protein 2 homolog (2 entities in total)
• 機能のキーワード: mtor, mtorc1, lst2, zfyve28, egfr, tos, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 249369.13

構造登録者

Craigie, L.M.,Maier, T. (登録日: 2024-04-26, 公開日: 2024-08-14, 最終更新日: 2024-08-28)

主引用文献

Battaglioni, S.,Craigie, L.M.,Filippini, S.,Maier, T.,Hall, M.N.
mTORC1 phosphorylates and stabilizes LST2 to negatively regulate EGFR.
Proc.Natl.Acad.Sci.USA, 121:e2405959121-e2405959121, 2024

PubMed Abstract: TORC1 (target of rapamycin complex 1) is a highly conserved protein kinase that plays a central role in regulating cell growth. Given the role of mammalian TORC1 (mTORC1) in metabolism and disease, understanding mTORC1 downstream signaling and feedback loops is important. mTORC1 recognizes some of its substrates via a five amino acid binding sequence called the TOR signaling (TOS) motif. mTORC1 binding to a TOS motif facilitates phosphorylation of a distinct, distal site. Here, we show that LST2, also known as ZFYVE28, contains a TOS motif (amino acids 401 to 405) and is directly phosphorylated by mTORC1 at serine 670 (S670). mTORC1-mediated S670 phosphorylation promotes LST2 monoubiquitination on lysine 87 (K87). Monoubiquitinated LST2 is stable and displays a broad reticular distribution. When mTORC1 is inactive, unphosphorylated LST2 is degraded by the proteasome. The absence of LST2 enhances EGFR (epidermal growth factor receptor) signaling. We propose that mTORC1 negatively feeds back on its upstream receptor EGFR via LST2.

PubMed: 39141345
DOI: 10.1073/pnas.2405959121

実験手法

ELECTRON MICROSCOPY (3.49 Å)