Norman Zhu1, W. Eric Rogers1, David K. Heidary2 and Tom Huxford1 1Structural Biochemistry Laboratory, Department of Chemistry and Biochemistry, San Diego State University, San Diego, California 92182, USA; 2Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27607, USA Corresponding author: thuxfordsdsu.edu Abstract

As part of the efforts to understand nuclear IκB function in NF-κB-dependent gene expression, we report an X-ray crystal structure of the IκBζ ankyrin repeat domain in complex with the dimerization domain of the NF-κB p50 homodimer. IκBζ possesses an N-terminal α helix that conveys domain folding stability. Affinity and specificity of the complex depend on a small portion of p50 at the nuclear localization signal. The model suggests that only one p50 subunit supports binding with IκBζ, and biochemical experiments confirm that IκBζ associates with DNA-bound NF-κB p50:RelA heterodimers. Comparisons of IκBζ:p50 and p50:κB DNA complex crystallographic models indicate that structural rearrangement is necessary for ternary complex formation of IκBζ and p50 with DNA.

Received May 4, 2024. Accepted June 13, 2024.