5CUF: X-ray Crystal Structure Of Semet Human Sestrin2

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.
PDB ID: 5CUFDownload
MMDB ID: 135457
PDB Deposition Date: 2015/7/24
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 3.5  Å
Source Organism:
Similar Structures:
Biological Unit for 5CUF: monomeric; determined by author
Molecular Components in 5CUF
Label Count Molecule
Protein (1 molecule)
Sestrin-2(Gene symbol: SESN2)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB