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Architecture of the human KICSTOR and GATOR1-KICSTOR complexes

ABSTRACT: Our understanding of the molecular processes by which cells sense nutrients has seen rapid progress, largely due to new structural andfunctional insights into the mTORC1 pathway. Serving as a key regulator of cellular growth, mTORC1 coordinates various environmental signalssuch as growth factors, nutrients, and energy status, and then converts these signals into responses that promote cell growth and inhibits catabolic processes. The KICSTOR complex is required for lysosomal recruitment of GATOR1, the key mTORC1 repressor. Genetic mutations inthe KICSTOR subunits are linked with severe human neurodevelopmental and epileptic encephalopathy. We combined Cryo-EM and in silicopredictions to assemble the structural models of KICSTOR and GATOR1-KICSTOR supercomplexes. SZT2 exhibits a long crescent-shapedarchitecture, which is built from tandem structured units connected via loops while anchoring other three subunits, including the ITFG2-KPTNheterodimer and C12orf66, to its C-terminal portion. GATOR1 interacts exclusively with the N-terminal domain (NTD) of SZT2. Our workprovides mechanistic insights into the molecular basis of how KICSTOR recruits GATOR1 on the lysosomal surface to regulate the nutrient-dependent signaling of mTORC1.

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ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Goran Stjepanovic

LAB HEAD: Goran Stjepanovic

PROVIDER: PXD060391 | Pride | 2025-09-20

REPOSITORIES: Pride

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			Action	DRS
	KIC-G2.raw	Raw
	KIC-G2_b.pep.xml	Pepxml
	KIC-G2_b.raw	Raw
	KIC-G2_b.xlsx	Xlsx
	KIC-G2_b_1.pep.xml	Pepxml

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