The X-ray crystal structure of the NF-κB p50·p65 heterodimer bound to the interferon β-κB site

Abstract

We have determined the x-ray crystal structure of the transcription factor NF-κB p50·p65 heterodimer complexed to ′B DNA from the cytokine interferon & enhancer (IFN&-′B). To better understand how the binding modes of NF-κB on its two best studied DNA targets might contribute to promoter-specific transcription, this structure is compared with the previously determined complex crystal structure containing NF-κB bound to the Ig κ light chain gene enhancer as well as to a second NF-κB·Ig κ light chain gene enhancer complex also reported in this paper. The global binding modes of all NF-κB·DNA complex structures are similar, although crystal-packing interactions lead to differences between identical complexes of the same crystallographic asymmetric unit. An extensive network of stacked amino acid side chains that contribute to base-specific DNA contacts is conserved among the three complexes. Consistent with earlier reports, however, the IFNβ-κB DNA is bent significantly less by NF-κB than is the Ig κ light chain gene enhancer. This and other small structural changes may play a role in explaining why NF-κB-directed transcription is sensitive to the context of specific promoters. The precise molecular mechanism behind the involvement of the high mobility group protein I(Y) in interferon β enhanceosome formation remains elusive.