7W7L

Structure of NF-kB p52 homodimer bound to 13-mer A/T-centric P-Selectin kB DNA fragment

Summary for 7W7L

• Entry DOI: 10.2210/pdb7w7l/pdb
• Descriptor: Nuclear factor NF-kappa-B p52 subunit, DNA (5'-D(*GP*GP*GP*GP*GP*TP*AP*AP*CP*CP*CP*CP*T)-3'), DNA (5'-D(*AP*GP*GP*GP*GP*TP*TP*AP*CP*CP*CP*CP*C)-3'), ... (4 entities in total)
• Functional Keywords: dna-protein complex, transcription factor, transcription, dna binding protein, dna binding protein-dna complex, dna binding protein-dna-dna complex, dna binding protein-dna/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 81424.81

Authors

Meshcheryakov, V.A.,Wang, V.Y.-F. (deposition date: 2021-12-05, release date: 2022-01-26, Last modification date: 2023-11-29)

Primary citation

Pan, W.,Meshcheryakov, V.A.,Li, T.,Wang, Y.,Ghosh, G.,Wang, V.Y.
Structures of NF-kappa B p52 homodimer-DNA complexes rationalize binding mechanisms and transcription activation.
Elife, 12:-, 2023

PubMed Abstract: The mammalian NF-κB p52:p52 homodimer together with its cofactor Bcl3 activates transcription of κB sites with a central G/C base pair (bp), while it is inactive toward κB sites with a central A/T bp. To understand the molecular basis for this unique property of p52, we have determined the crystal structures of recombinant human p52 protein in complex with a P-selectin(PSel)-κB DNA (5'-GGGGTACCCC-3') (central bp is underlined) and variants changing the central bp to A/T or swapping the flanking bp. The structures reveal a nearly two-fold widened minor groove in the central region of the DNA as compared to all other currently available NF-κB-DNA complex structures, which have a central A/T bp. Microsecond molecular dynamics (MD) simulations of free DNAs and p52 bound complexes reveal that free DNAs exhibit distinct preferred conformations, and p52:p52 homodimer induces the least amount of DNA conformational changes when bound to the more transcriptionally active natural G/C-centric PSel-κB, but adopts closed conformation when bound to the mutant A/T and swap DNAs due to their narrowed minor grooves. Our binding assays further demonstrate that the fast kinetics favored by entropy is correlated with higher transcriptional activity. Overall, our studies have revealed a novel conformation for κB DNA in complex with NF-κB and pinpoint the importance of binding kinetics, dictated by DNA conformational and dynamic states, in controlling transcriptional activation for NF-κB.

PubMed: 36779700
DOI: 10.7554/eLife.86258

Experimental method

X-RAY DIFFRACTION (3 Å)