6WKW

EM structure of CtBP2 with a minimal dehydrogenase domain of CtBP2

Summary for 6WKW

• Entry DOI: 10.2210/pdb6wkw/pdb
• EMDB information: 21811
• Descriptor: C-terminal-binding protein 2, NICOTINAMIDE-ADENINE-DINUCLEOTIDE (2 entities in total)
• Functional Keywords: transcriptional corepression, cancer, gene repression, metabolic sensor, gene regulation
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 149136.56

Authors

Jecrois, A.M. (deposition date: 2020-04-17, release date: 2020-12-02, Last modification date: 2025-06-04)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.6 Å)