8U9L

Crystal Structure of RelA-cRel chimera complex with DNA

Summary for 8U9L

• Entry DOI: 10.2210/pdb8u9l/pdb
• Descriptor: DNA (5'-D(P*TP*TP*GP*AP*TP*GP*GP*GP*AP*AP*TP*TP*TP*CP*CP*GP*AP*TP*TP*C)-3'), DNA (5'-D(P*GP*AP*AP*TP*CP*GP*GP*AP*AP*AP*TP*TP*CP*CP*CP*AP*TP*CP*AP*A)-3'), Transcription factor p65,Proto-oncogene c-Rel chimera (3 entities in total)
• Functional Keywords: vertebrate evolution, transcription factor, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 16
• Total formula weight: 300830.54

Authors

Chang, A.,Wu, Y.,Li, S.X.,Smale, S.,Chen, L. (deposition date: 2023-09-19, release date: 2024-10-02, Last modification date: 2025-05-14)

Primary citation

Daly, A.E.,Chang, A.B.,Purbey, P.K.,Williams, K.J.,Li, S.,Redelings, B.D.,Yeh, G.,Wu, Y.,Pope, S.D.,Venkatesh, B.,Li, S.,Nguyen, K.,Rodrigues, J.,Jorgensen, K.,Dasgupta, A.,Siggers, T.,Chen, L.,Smale, S.T.
Stepwise neofunctionalization of the NF-kappa B family member Rel during vertebrate evolution.
Nat.Immunol., 26:760-774, 2025

PubMed Abstract: Adaptive immunity and the five vertebrate NF-κB family members first emerged in cartilaginous fish, suggesting that NF-κB family divergence helped to facilitate adaptive immunity. One specialized function of the NF-κB Rel protein in macrophages is activation of Il12b, which encodes a key regulator of T cell development. We found that Il12b exhibits much greater Rel dependence than inducible innate immunity genes in macrophages, with the unique function of Rel dimers depending on a heightened intrinsic DNA-binding affinity. Chromatin immunoprecipitation followed by sequencing experiments defined differential DNA-binding preferences of NF-κB family members genome-wide, and X-ray crystallography revealed a key residue that supports the heightened DNA-binding affinity of Rel dimers. Unexpectedly, this residue, the heightened affinity of Rel dimers, and the portion of the Il12b promoter bound by Rel dimers were largely restricted to mammals. Our findings reveal major structural transitions in an NF-κB family member and one of its key target promoters at a late stage of vertebrate evolution that apparently contributed to immunoregulatory rewiring in mammalian species.

PubMed: 40307452
DOI: 10.1038/s41590-025-02138-2

Experimental method

X-RAY DIFFRACTION (3.091 Å)