5YTK

Crystal structure of SIRT3 bound to a leucylated AceCS2

Summary for 5YTK

• Entry DOI: 10.2210/pdb5ytk/pdb
• Descriptor: NAD-dependent protein deacetylase sirtuin-3, mitochondrial, AceCS2-KLeu, ZINC ION, ... (6 entities in total)
• Functional Keywords: dna-dependent deacetylase sirtuin-3, leucylated acecs2, hydrolase
• Biological source: Homo sapiens (Human); More
• Cellular location: Mitochondrion matrix : Q9NTG7
• Total number of polymer chains: 10
• Total formula weight: 188193.80

Authors

Li, J.,Gong, W.,Xu, Y. (deposition date: 2017-11-18, release date: 2017-12-27, Last modification date: 2024-11-13)

Primary citation

He, X.D.,Gong, W.,Zhang, J.N.,Nie, J.,Yao, C.F.,Guo, F.S.,Lin, Y.,Wu, X.H.,Li, F.,Li, J.,Sun, W.C.,Wang, E.D.,An, Y.P.,Tang, H.R.,Yan, G.Q.,Yang, P.Y.,Wei, Y.,Mao, Y.Z.,Lin, P.C.,Zhao, J.Y.,Xu, Y.,Xu, W.,Zhao, S.M.
Sensing and Transmitting Intracellular Amino Acid Signals through Reversible Lysine Aminoacylations
Cell Metab., 27:151-166.e6, 2018

PubMed Abstract: Amino acids are known regulators of cellular signaling and physiology, but how they are sensed intracellularly is not fully understood. Herein, we report that each aminoacyl-tRNA synthetase (ARS) senses its cognate amino acid sufficiency through catalyzing the formation of lysine aminoacylation (K-AA) on its specific substrate proteins. At physiologic levels, amino acids promote ARSs bound to their substrates and form K-AAs on the ɛ-amine of lysines in their substrates by producing reactive aminoacyl adenylates. The K-AA marks can be removed by deacetylases, such as SIRT1 and SIRT3, employing the same mechanism as that involved in deacetylation. These dynamically regulated K-AAs transduce signals of their respective amino acids. Reversible leucylation on ras-related GTP-binding protein A/B regulates activity of the mammalian target of rapamycin complex 1. Glutaminylation on apoptosis signal-regulating kinase 1 suppresses apoptosis. We discovered non-canonical functions of ARSs and revealed systematic and functional amino acid sensing and signal transduction networks.

PubMed: 29198988
DOI: 10.1016/j.cmet.2017.10.015

Experimental method

X-RAY DIFFRACTION (2.7 Å)