Janus-faced Sestrin2 controls ROS and mTOR signalling through two separate functional domains

Hanseong Kim, Sojin An, Seung-Hyun Ro, Filipa Teixeira, Gyeong Jin Park, Cheal Kim, Chun-Seok Cho, Jeong-Sig Kim, Ursula Jakob, Jun Hee Lee () and Uhn-Soo Cho ()
Additional contact information
Hanseong Kim: University of Michigan
Sojin An: University of Michigan
Seung-Hyun Ro: University of Michigan
Filipa Teixeira: Cellular and Developmental Biology, University of Michigan
Gyeong Jin Park: University of Michigan
Cheal Kim: Seoul National University of Science and Technology
Chun-Seok Cho: University of Michigan
Jeong-Sig Kim: University of Michigan
Ursula Jakob: University of Michigan
Jun Hee Lee: University of Michigan
Uhn-Soo Cho: University of Michigan

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: 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.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms10025 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms10025

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms10025

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().