7VKR

Crystal structure of D. melanogaster SAMTOR in complex with SAM

Summary for 7VKR

• Entry DOI: 10.2210/pdb7vkr/pdb
• Descriptor: S-adenosylmethionine sensor upstream of mTORC1, S-ADENOSYLMETHIONINE, CITRIC ACID, ... (4 entities in total)
• Functional Keywords: samtor, transferase, sam
• Biological source: Drosophila melanogaster (Fruit fly)
• Total number of polymer chains: 4
• Total formula weight: 143531.84

Authors

Tang, X.,Zhang, T.,Ding, J. (deposition date: 2021-09-30, release date: 2022-07-20, Last modification date: 2024-11-13)

Primary citation

Tang, X.,Zhang, Y.,Wang, G.,Zhang, C.,Wang, F.,Shi, J.,Zhang, T.,Ding, J.
Molecular mechanism of S -adenosylmethionine sensing by SAMTOR in mTORC1 signaling.
Sci Adv, 8:eabn3868-eabn3868, 2022

PubMed Abstract: The mechanistic target of rapamycin-mLST8-raptor complex (mTORC1) functions as a central regulator of cell growth and metabolism in response to changes in nutrient signals such as amino acids. SAMTOR is an -adenosylmethionine (SAM) sensor, which regulates the mTORC1 activity through its interaction with the GTPase-activating protein activity toward Rags-1 (GATOR1)-KPTN, ITFG2, C12orf66 and SZT2-containing regulator (KICSTOR) complex. In this work, we report the crystal structures of SAMTOR in apo form and in complex with SAM. SAMTOR comprises an N-terminal helical domain and a C-terminal SAM-dependent methyltransferase (MTase) domain. The MTase domain contains the SAM-binding site and the potential GATOR1-KICSTOR-binding site. The helical domain functions as a molecular switch, which undergoes conformational change upon SAM binding and thereby modulates the interaction of SAMTOR with GATOR1-KICSTOR. The functional roles of the key residues and the helical domain are validated by functional assays. Our structural and functional data together reveal the molecular mechanism of the SAM sensing of SAMTOR and its functional role in mTORC1 signaling.

PubMed: 35776786
DOI: 10.1126/sciadv.abn3868

Experimental method

X-RAY DIFFRACTION (2.1 Å)