[대학원 생명과학과 세미나 안내]
연사 : 조운수 교수 (University of Michigan Medical School, Biological Chemistry Department)
연제 : Janus-faced Sestrin2 controls ROS and mTOR signaling through two separate functional domains
일시 : 2016년 6월 29일 (수) 오전 10시30분
장소 : 하나과학관 A동 207호
초청교수 : 송현규 교수
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 fulfill this dual role has remained elusive so far. Here, we report the crystal structure of human Sestrin2 (hSesn2), and show that hSesn2 is two-fold 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 production and mTORC1 activity.