Cryo-EM structure of the SEA complex

Article Article scientifique Article Cryo-EM structure of the SEA complex eng 2022-10-26 2022-10-26 author Tafur Petrozzi Lucas 0000-0002-6618-9649 908490 author Hinterndorfer Kerstin 925092 author Gabus Caroline 692546 author Lamanna Chiara 840505 author Bergmann Arianne 88627 author Sadian Yashar 917818 author Hamdi Farzad 0000-0002-2155-5000 author Kyrilis Fotis L. 0000-0002-4040-6289 author Kastritis Panagiotis L. 0000-0002-1463-8422 author Loewith Robbie Joséph 0000-0002-2482-603X 630703 399-404 10.1038/s41586-022-05370-0 36289347 0028-0836 PMC9646525 https://www.nature.com/articles/s41586-022-05370-0 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 1 . Functionally, the SEAC has been divided into two subcomplexes: SEACIT, which has GAP activity and inhibits TORC1, and SEACAT, which regulates SEACIT 2 . This system is conserved in mammals: the GATOR complex, consisting of GATOR1 (SEACIT) and GATOR2 (SEACAT), transmits amino acid 3 and glucose 4 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. Dewey 570 7daed2ee-1311-4824-9df9-2e51260a966a Département de biologie moléculaire et cellulaire 16484 false 814 Groupe Loewith Nature 611 7935 45fd9bf8-c9d7-4776-8bc4-7a42c43e079c Article (Published version) Public Article-scientifique-from-crossref.pdf 26660748 application/pdf openAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire et cellulaire

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Cryo-EM structure of the SEA complex	Nature			2022	233	109

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Lamanna, Chiara