2RAM

A novel DNA recognition mode by the NF-kappa B p65 homodimer.

(1998) Nat Struct Biol 5: 67-73

• PubMed: 9437432 Search on PubMed
• DOI: https://doi.org/10.1038/nsb0198-67
• Primary Citation of Related Structures:  
  1RAM, 2RAM


• PubMed Abstract: 
  

  The crystal structure of the NF-kappa B p65 (RelA) homodimer in complex with a DNA target has been determined to 2.4 A resolution. The two p65 subunits are not symmetrically disposed on the DNA target. The homodimer should optimally bind to a pseudo-palindromic nine base pair target with each subunit recognizing a 5'GGAA-3' half site separated by a central A-T base pair. However, one of the subunits (subunit B) encounters a half site of 5'-GAAA-3'. The single base-pair change from G-C to A-T results in highly unfavorable interactions between this half site and the base contacting protein residues in subunit B, which leads to an 18 degrees rotation of the N-terminal terminal domain from its normal conformation. Remarkably, subunit B retains all the interactions with the sugar phosphate backbone of the DNA target. This mode of interaction allows the NF-kappa B p65 homodimer to recognize DNA targets containing only one cognate half site. Differences in the sequence of the other half site provide variations in conformation and affinity of the complex.

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Organizational Affiliation: 

Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093-0359, USA.