3NGN

Crystal structure of the human CNOT6L nuclease domain in complex with AMP

3NGN の概要

• エントリーDOI: 10.2210/pdb3ngn/pdb
• 関連するPDBエントリー: 3NGO 3NGQ
• 分子名称: CCR4-NOT transcription complex subunit 6-like, ADENOSINE MONOPHOSPHATE (3 entities in total)
• 機能のキーワード: protein-amp complex, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q96LI5
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 45834.94

構造登録者

Wang, H.,Morita, M.,Yang, W.,Bartlam, M.,Yamamoto, T.,Rao, Z. (登録日: 2010-06-12, 公開日: 2010-07-28, 最終更新日: 2024-03-20)

主引用文献

Wang, H.,Morita, M.,Yang, X.,Suzuki, T.,Yang, W.,Wang, J.,Ito, K.,Wang, Q.,Zhao, C.,Bartlam, M.,Yamamoto, T.,Rao, Z.
Crystal structure of the human CNOT6L nuclease domain reveals strict poly(A) substrate specificity.
Embo J., 2010

PubMed Abstract: CCR4, an evolutionarily conserved member of the CCR4-NOT complex, is the main cytoplasmic deadenylase. It contains a C-terminal nuclease domain with homology to the endonuclease-exonuclease-phosphatase (EEP) family of enzymes. We have determined the high-resolution three-dimensional structure of the nuclease domain of CNOT6L, a human homologue of CCR4, by X-ray crystallography using the single-wavelength anomalous dispersion method. This first structure of a deadenylase belonging to the EEP family adopts a complete alpha/beta sandwich fold typical of hydrolases with highly conserved active site residues similar to APE1. The active site of CNOT6L should recognize the RNA substrate through its negatively charged surface. In vitro deadenylase assays confirm the critical active site residues and show that the nuclease domain of CNOT6L exhibits full Mg(2+)-dependent deadenylase activity with strict poly(A) RNA substrate specificity. To understand the structural basis for poly(A) RNA substrate binding, crystal structures of the CNOT6L nuclease domain have also been determined in complex with AMP and poly(A) DNA. The resulting structures suggest a molecular deadenylase mechanism involving a pentacovalent phosphate transition.

PubMed: 20628353
DOI: 10.1038/emboj.2010.152

実験手法

X-RAY DIFFRACTION (2.4 Å)