9WRJ

Crystal structure of CtBP1 in complex with PALI1

Summary for 9WRJ

• Entry DOI: 10.2210/pdb9wrj/pdb
• Related: 9WRI
• Descriptor: C-terminal-binding protein 1, Ligand-dependent corepressor, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (4 entities in total)
• Functional Keywords: complex, protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 41481.77

Authors

Zhang, B.,Jiang, J.,Sun, W.,Cai, Q.,Chen, S. (deposition date: 2025-09-12, release date: 2026-01-28)

Primary citation

Zhang, B.,Jiang, J.,Chen, P.,Lin, C.,Sun, W.,Wang, J.,Li, W.,Chen, J.,Luo, Q.,Cai, D.,Cai, Q.,Chen, S.
PALI1 enhances CtBP1/2 oligomerization and couples CtBP1/2 to PRC2.
Biochem.Biophys.Res.Commun., 800:153295-153295, 2026

PubMed Abstract: Polycomb Repressive Complex 2 (PRC2) and C-terminal binding proteins 1 and 2 (CtBP1/2) are key epigenetic regulators that frequently co-occupy chromatin, yet their crosstalk remains poorly understood. Here, we delineate the molecular basis of the interaction between CtBP1/2 and the N-terminal domain of PALI1, an accessory subunit of PRC2. The PALI1 N-terminus contains two DLS-like motifs that bind CtBP1/2 bivalently, enhancing affinity and promoting higher-order oligomerization. Conversely, disruption of CtBP1/2 oligomerization weakens PALI1 binding, revealing a reciprocal mechanism stabilizing the CtBP1/2-PALI1 complex. The 2.20 Å structure of the CtBP1-PALI1 complex reveals the detailed interaction interface, which, together with biochemical data, supports a model where tandem DLS-like motifs drive CtBP1/2 oligomerization and multivalent engagement. Through its C-terminal PRC2-binding domain, PALI1 acts as a dual-interface scaffold linking CtBP1/2 and PRC2, providing a structural framework for their coordinated chromatin recruitment and transcriptional repression.

PubMed: 41547303
DOI: 10.1016/j.bbrc.2026.153295

Experimental method

X-RAY DIFFRACTION (2.2 Å)