8AE6

Cryo-EM structure of the SEA complex wing (SEACIT)

8AE6 の概要

• エントリーDOI: 10.2210/pdb8ae6/pdb
• 関連するPDBエントリー: 8ADL
• EMDBエントリー: 15364 15373 15374 15381
• 分子名称: Nitrogen permease regulator 3, Maintenance of telomere capping protein 5, Vacuolar membrane-associated protein IML1, ... (4 entities in total)
• 機能のキーワード: gtpase activating protein, torc1, rag gtpase, signaling protein
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 513386.06

構造登録者

Tafur, L.,Loewith, R. (登録日: 2022-07-12, 公開日: 2022-11-02, 最終更新日: 2024-07-24)

主引用文献

Tafur, L.,Hinterndorfer, K.,Gabus, C.,Lamanna, C.,Bergmann, A.,Sadian, Y.,Hamdi, F.,Kyrilis, F.L.,Kastritis, P.L.,Loewith, R.
Cryo-EM structure of the SEA complex.
Nature, 611:399-404, 2022

PubMed Abstract: The SEA complex (SEAC) is a growth regulator that acts as a GTPase-activating protein (GAP) towards Gtr1, a Rag GTPase that relays nutrient status to the Target of Rapamycin Complex 1 (TORC1) in yeast. Functionally, the SEAC has been divided into two subcomplexes: SEACIT, which has GAP activity and inhibits TORC1, and SEACAT, which regulates SEACIT. This system is conserved in mammals: the GATOR complex, consisting of GATOR1 (SEACIT) and GATOR2 (SEACAT), transmits amino acid and glucose signals to mTORC1. Despite its importance, the structure of SEAC/GATOR, and thus molecular understanding of its function, is lacking. Here, we solve the cryo-EM structure of the native eight-subunit SEAC. The SEAC has a modular structure in which a COPII-like cage corresponding to SEACAT binds two flexible wings, which correspond to SEACIT. The wings are tethered to the core via Sea3, which forms part of both modules. The GAP mechanism of GATOR1 is conserved in SEACIT, and GAP activity is unaffected by SEACAT in vitro. In vivo, the wings are essential for recruitment of the SEAC to the vacuole, primarily via the EGO complex. Our results indicate that rather than being a direct inhibitor of SEACIT, SEACAT acts as a scaffold for the binding of TORC1 regulators.

PubMed: 36289347
DOI: 10.1038/s41586-022-05370-0

実験手法

ELECTRON MICROSCOPY (2.7 Å)