Amanda J. Fusco1, D. Huang1, D. Josh Miller1, Vivien Ya‐Fan Wang1, Don Vu1, Gourisankar Ghosh1
1Department of Chemistry & Biochemistry, University of California at San Diego San Diego, 9500 Gilman Drive La Jolla California 92093 USA
Tóm tắt
The X‐ray structure of the nuclear factor‐κB (NF‐κB) p52:RelB:κB DNA complex reveals a new recognition feature not previously seen in other NF‐κB:κB DNA complexes. Arg 125 of RelB is in contact with an additional DNA base pair. Surprisingly, the p52:RelB R125A mutant heterodimer shows defects both in DNA binding and in transcriptional activity only to a subclass of κB sites. We found that the Arg 125‐sensitive κB sites contain more contiguous and centrally located A:T base pairs than do the insensitive sites. A protein‐induced kink observed in this complex, which used an AT‐rich κB site, might allow the DNA contact by Arg 125; such a kink might not be possible in complexes with non‐AT‐rich κB sites. Furthermore, we show that the p52:RelB heterodimer binds to a broader spectrum of κB sites when compared with the p50:RelA heterodimer. We suggest that the p52:RelB heterodimer is more adaptable to complement sequence and structural variations in κB sites when compared with other NF‐κB dimers.
