NF-kappaB p52:RelB heterodimer recognizes two classes of kappaB sites with two distinct modes.
The X-ray structure of the nuclear factor-kappaB (NF-kappaB) p52:RelB:kappaB DNA complex reveals a new recognition feature not previously seen in other NF-kappaB:kappaB 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 kappaB sites. We found that the Arg 125-sensitive kappaB 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 kappaB site, might allow the DNA contact by Arg 125; such a kink might not be possible in complexes with non-AT-rich kappaB sites. Furthermore, we show that the p52:RelB heterodimer binds to a broader spectrum of kappaB 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 kappaB sites when compared with other NF-kappaB dimers.
Fusco
Amanda J
AJ
Department of Chemistry & Biochemistry, University of California at San Diego, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Huang
De-Bin
DB
Miller
Dustyn
D
Wang
Vivien Ya-Fan
VY
Vu
Don
D
Ghosh
Gourisankar
G
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001482:Base Composition; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D052003:NF-kappa B p52 Subunit / Q000737:chemistry*; D017354:Point Mutation; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D051841:Transcription Factor RelB / Q000737:chemistry*; D014158:Transcription, Genetic
D052003:NF-kappa B p52 Subunit; C498206:NFKB2 protein, human; C497594:Relb protein, mouse; D051841:Transcription Factor RelB; D004247:DNA