9CB5

Crystal structure of nucleolin in complex with MYC promoter G-quadruplex

Summary for 9CB5

• Entry DOI: 10.2210/pdb9cb5/pdb
• Descriptor: Nucleolin, MYC promoter G-quadruplex, Fab heavy chain, ... (6 entities in total)
• Functional Keywords: myc g-quadruplex, nucleolin, modular protein, transcription factor, g4-epigenetic, transcription, transcription-dna complex, transcription/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 194439.92

Authors

Chen, L.,Dickerhoff, J.,Noinaj, N.,Yang, D. (deposition date: 2024-06-18, release date: 2025-04-30)

Primary citation

Chen, L.,Dickerhoff, J.,Zheng, K.W.,Erramilli, S.,Feng, H.,Wu, G.,Onel, B.,Chen, Y.,Wang, K.B.,Carver, M.,Lin, C.,Sakai, S.,Wan, J.,Vinson, C.,Hurley, L.,Kossiakoff, A.A.,Deng, N.,Bai, Y.,Noinaj, N.,Yang, D.
Structural basis for nucleolin recognition of MYC promoter G-quadruplex.
Science, 388:eadr1752-eadr1752, 2025

PubMed Abstract: The oncogene promoter G-quadruplex (MycG4) regulates transcription and is a prevalent G4 locus in immortal cells. Nucleolin, a major MycG4-binding protein, exhibits greater affinity for MycG4 than for nucleolin recognition element (NRE) RNA. Nucleolin's four RNA binding domains (RBDs) are essential for high-affinity MycG4 binding. We present the 2.6-angstrom crystal structure of the nucleolin-MycG4 complex, revealing a folded parallel three-tetrad G-quadruplex with two coordinating potassium ions (K), interacting with RBD1, RBD2, and Linker12 through its 6-nucleotide (nt) central loop and 5' flanking region. RBD3 and RBD4 bind MycG4's 1-nt loops as demonstrated by nuclear magnetic resonance (NMR). Cleavage under targets and tagmentation sequencing confirmed nucleolin's binding to MycG4 in cells. Our results revealed a G4 conformation-based recognition by a regulating protein through multivalent interactions, suggesting that G4s are nucleolin's primary cellular substrates, indicating G4 epigenetic transcriptional regulation and helping G4-targeted drug discovery.

PubMed: 40245140
DOI: 10.1126/science.adr1752

Experimental method

X-RAY DIFFRACTION (2.6 Å)