5CUF

X-ray crystal structure of SeMet human Sestrin2

Summary for 5CUF

• Entry DOI: 10.2210/pdb5cuf/pdb
• Descriptor: Sestrin-2 (1 entity in total)
• Functional Keywords: alkylhydroperoxidase, oxidoreductase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 5
• Total formula weight: 277212.29

Authors

Kim, H.,An, S.,Ro, S.-H.,Lee, J.H.,Cho, U.-S. (deposition date: 2015-07-24, release date: 2016-01-13, Last modification date: 2024-10-16)

Primary citation

Kim, H.,An, S.,Ro, S.H.,Teixeira, F.,Jin Park, G.,Kim, C.,Cho, C.S.,Kim, J.S.,Jakob, U.,Hee Lee, J.,Cho, U.S.
Janus-faced Sestrin2 controls ROS and mTOR signalling through two separate functional domains.
Nat Commun, 6:10025-10025, 2015

PubMed Abstract: Sestrins are stress-inducible metabolic regulators with two seemingly unrelated but physiologically important functions: reduction of reactive oxygen species (ROS) and inhibition of the mechanistic target of rapamycin complex 1 (mTORC1). How Sestrins fulfil this dual role has remained elusive so far. Here we report the crystal structure of human Sestrin2 (hSesn2), and show that hSesn2 is twofold pseudo-symmetric with two globular subdomains, which are structurally similar but functionally distinct from each other. While the N-terminal domain (Sesn-A) reduces alkylhydroperoxide radicals through its helix-turn-helix oxidoreductase motif, the C-terminal domain (Sesn-C) modified this motif to accommodate physical interaction with GATOR2 and subsequent inhibition of mTORC1. These findings clarify the molecular mechanism of how Sestrins can attenuate degenerative processes such as aging and diabetes by acting as a simultaneous inhibitor of ROS accumulation and mTORC1 activation.

PubMed: 26612684
DOI: 10.1038/ncomms10025

Experimental method

X-RAY DIFFRACTION (3.5 Å)