Structure and function of the yeast amino acid-sensing SEAC

Article Article scientifique Article Structure and function of the yeast amino acid-sensing SEAC–EGOC supercomplex eng 2026-02-12 author Tafur Petrozzi Lucas 0000-0002-6618-9649 Department of Molecular and Cellular Biology, University of Geneva, Geneva, Switzerland. ltafur@cnio.es.,Structural Mechanisms of Cell Growth Group, Structural Biology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. ltafur@cnio.es. 908490 author Bonadei Lenny 0000-0002-6581-7551 Department of Molecular and Cellular Biology, University of Geneva, Geneva, Switzerland. 841388 Département de biologie moléculaire et cellulaire (MOCEL) author Zheng Yiqiang Department of Molecular and Cellular Biology, University of Geneva, Geneva, Switzerland. 408280 Département de biologie moléculaire et cellulaire (MOCEL) author Gabus Caroline Department of Molecular and Cellular Biology, University of Geneva, Geneva, Switzerland. 692546 author Loewith Robbie Joséph 0000-0002-2482-603X Department of Molecular and Cellular Biology, University of Geneva, Geneva, Switzerland. robbie.loewith@unige.ch. 630703 Département de biologie moléculaire et cellulaire (MOCEL) 10.1038/s41594-026-01746-2 41680390 1545-9985 https://www.nature.com/articles/s41594-026-01746-2 The Seh1-associated complex (SEAC; GATOR in mammals) transduces amino acid signals to the Target of Rapamycin Complex 1 (TORC1), a master regulator of cell growth. The SEAC is composed of two subcomplexes, SEACIT (GATOR1), an inhibitor of TORC1 that has GAP activity against Gtr1, and SEACAT (GATOR2), which appears to regulate SEACIT. However, the molecular details of this regulation are unclear. Here we determined the cryo-electron microscopy structure of the SEAC bound to its substrate, the EGOC (Ragulator-Rag), and studied its function in TORC1 amino acid signaling. A single SEAC can interact with two EGOC molecules via SEACIT, binding exclusively to the 'active' version of the EGOC, without involvement of SEACAT. The GAP activity of the SEACIT is essential for the regulation of TORC1 by amino acids and its loss phenocopies the lack of Gtr1-Gtr2, establishing the SEAC-EGOC complex as an amino acid-sensing hub. Compared to other SEACAT subunits, the loss of Sea2, or its N-terminal β-propeller domain, yielded strong defects in amino acid signaling to TORC1. Our results suggest that the Sea2 β-propeller recruits a GAP inhibitor to mediate fast amino acid signaling to TORC1, with additional pathways acting with slower kinetics. Dewey 570 7daed2ee-1311-4824-9df9-2e51260a966a Département de biologie moléculaire et cellulaire 16484 false 814 Groupe Loewith Nature structural & molecular biology 24066c26-a0b7-4f2a-afb2-b6707e27d948 Article (Published version) Public Article_scientifique_from_crossref.pdf 25182372 application/pdf CC BY-NC-ND-4.0 43a01b5b533d51c3f7810f61c2a9e7690f1a7404654bdc04384f9df7e170aa5d openAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire et cellulaire

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Structure and function of the yeast amino acid-sensing SEAC–EGOC supercomplex	Nature structural & molecular biology			2026	4	47

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