Cryo-EM structure of the SEA complex.
Lucas Tafur1, Kerstin Hinterndorfer1, Caroline Gabus1
1Department of Molecular and Cellular Biology, University of Geneva, Geneva, Switzerland.
Nature
|October 26, 2022
Summary
The SEA complex (SEAC), a nutrient-sensing growth regulator, has a modular structure revealed by cryo-EM. SEACAT acts as a scaffold, not a direct inhibitor, for SEACIT, impacting TORC1 regulation.
Area of Science:
- Cellular biology
- Molecular mechanisms of nutrient sensing
- Protein complex structure and function
Background:
- The SEA complex (SEAC) and its mammalian counterpart, GATOR, regulate cell growth by relaying nutrient status to TORC1.
- SEAC comprises SEACIT (GAP activity) and SEACAT (regulatory), conserved in GATOR1 and GATOR2.
- The molecular structure and function of SEAC/GATOR remain poorly understood.
Purpose of the Study:
- To determine the cryo-EM structure of the native eight-subunit SEAC.
- To elucidate the structural basis for SEAC's function as a nutrient regulator.
- To understand the interplay between SEACIT and SEACAT in TORC1 signaling.
Main Methods:
- Cryo-electron microscopy (cryo-EM) to solve the structure of the native SEAC.
- Biochemical assays to assess GTPase-activating protein (GAP) activity.
- In vivo studies to investigate SEAC localization and function.
Main Results:
- The SEAC exhibits a modular architecture with a SEACAT cage binding SEACIT wings.
- Sea3 protein links SEACAT and SEACIT modules.
- SEACAT is a scaffold for TORC1 regulators, not a direct inhibitor of SEACIT's GAP activity.
- SEACIT's GAP activity is conserved and independent of SEACAT in vitro.
- SEAC wings are crucial for vacuolar recruitment via the EGO complex in vivo.
Conclusions:
- The cryo-EM structure reveals the modular organization of the SEAC.
- SEACAT functions as a scaffold, modulating SEACIT's role in nutrient signaling to TORC1.
- This structural insight provides a molecular basis for understanding nutrient sensing pathways.
