6WKW

EM structure of CtBP2 with a minimal dehydrogenase domain of CtBP2

6WKW の概要

• エントリーDOI: 10.2210/pdb6wkw/pdb
• EMDBエントリー: 21811
• 分子名称: C-terminal-binding protein 2, NICOTINAMIDE-ADENINE-DINUCLEOTIDE (2 entities in total)
• 機能のキーワード: transcriptional corepression, cancer, gene repression, metabolic sensor, gene regulation
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 149136.56

構造登録者

Jecrois, A.M. (登録日: 2020-04-17, 公開日: 2020-12-02, 最終更新日: 2025-06-04)

主引用文献

Jecrois, A.M.,Dcona, M.M.,Deng, X.,Bandyopadhyay, D.,Grossman, S.R.,Schiffer, C.A.,Royer Jr., W.E.
Cryo-EM structure of CtBP2 confirms tetrameric architecture.
Structure, 29:310-, 2021

PubMed Abstract: C-terminal binding proteins 1 and 2 (CtBP1 and CtBP2) are transcriptional regulators that activate or repress many genes involved in cellular development, apoptosis, and metastasis. NADH-dependent CtBP activation has been implicated in multiple types of cancer and poor patient prognosis. Central to understanding activation of CtBP in oncogenesis is uncovering how NADH triggers protein assembly, what level of assembly occurs, and if oncogenic activity depends upon such assembly. Here, we present the cryoelectron microscopic structures of two different constructs of CtBP2 corroborating that the native state of CtBP2 in the presence of NADH is tetrameric. The physiological relevance of the observed tetramer was demonstrated in cell culture, showing that CtBP tetramer-destabilizing mutants are defective for cell migration, transcriptional repression of E-cadherin, and activation of TIAM1. Together with our cryoelectron microscopy studies, these results highlight the tetramer as the functional oligomeric form of CtBP2.

PubMed: 33264605
DOI: 10.1016/j.str.2020.11.008

実験手法

ELECTRON MICROSCOPY (3.6 Å)