Sirt1 carboxyl-domain is an ATP-repressible domain that is transferrable to other proteins

• DOI: 10.1038/ncomms15560
• Publication Date: 2017-05-15T10:29:38Z
• Authors: Hyeog Kang; Shinichi Oka; Duck-Yeon Lee; Junhong Park; Angel M. Aponte; Young-Sang Jung; Jacob Bitterman; Peiyong Zhai; Yi He; Hamed Kooshapur; Rodolfo Ghirlando; Nico Tjandra; Sean B. Lee; Myung K. Kim; Junichi Sadoshima; Jay H. Chung
• Keywords: Sirtuin 1

Sirt1 is an NAD+-dependent protein deacetylase that regulates many physiological functions, including stress resistance, adipogenesis, cell senescence and energy production. can be activated by deprivation, but the mechanism poorly understood. Here, we report negatively regulated ATP, which binds to C-terminal domain (CTD) of Sirt1. ATP suppresses activity impairing CTD's ability bind as well its function substrate recruitment site. not NAD+, causes a conformational shift less compact structure. Mutations prevent binding increase Sirt1's promote resistance inhibit adipogenesis under high-ATP conditions. Interestingly, CTD attached other proteins, thereby converting them into energy-regulated proteins. These discoveries provide insight how extreme deprivation impact underscore complex nature structure regulation.