6SCX

Crystal structure of the catalytic domain of human NUDT12 in complex with 7-methyl-guanosine-5'-triphosphate

6SCX の概要

• エントリーDOI: 10.2210/pdb6scx/pdb
• 分子名称: Peroxisomal NADH pyrophosphatase NUDT12, CADMIUM ION, 7-METHYL-GUANOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: nudix protein, denadding enzyme, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 122628.90

構造登録者

McCarthy, A.A.,Chen, K.M.,Wu, H.,Li, L.,Homolka, D.,Gos, P.,Fleury-Olela, F.,Pillai, R.S. (登録日: 2019-07-25, 公開日: 2020-01-08, 最終更新日: 2024-11-06)

主引用文献

Wu, H.,Li, L.,Chen, K.M.,Homolka, D.,Gos, P.,Fleury-Olela, F.,McCarthy, A.A.,Pillai, R.S.
Decapping Enzyme NUDT12 Partners with BLMH for Cytoplasmic Surveillance of NAD-Capped RNAs.
Cell Rep, 29:4422-4434.e13, 2019

PubMed Abstract: RNA polymerase II transcripts receive a protective 5',5'-triphosphate-linked 7-methylguanosine (mG) cap, and its removal by decapping enzymes like DCP2 is critical for initiation of RNA decay. Alternative RNA caps can be acquired when transcription initiation uses metabolites like nicotinamide adenine dinucleotide (NAD), generating NAD-RNAs. Here, we identify human NUDT12 as a cytosolic NAD-RNA decapping enzyme. NUDT12 is active only as homodimers, with each monomer contributing to creation of the two functional catalytic pockets. We identify an ∼600-kDa dodecamer complex between bleomycin hydrolase (BLMH) and NUDT12, with BLMH being required for localization of NUDT12 to a few discrete cytoplasmic granules that are distinct from P-bodies. Both proteins downregulate gene expression when artificially tethered to a reporter RNA in vivo. Furthermore, loss of Nudt12 results in a significant upregulation of circadian clock transcripts in mouse liver. Overall, our study points to a physiological role for NUDT12 in the cytosolic surveillance of NAD-RNAs.

PubMed: 31875550
DOI: 10.1016/j.celrep.2019.11.108

実験手法

X-RAY DIFFRACTION (2.92 Å)