CRYSTAL-STRUCTURE OF P50 P65 HETERODIMER OF TRANSCRIPTION FACTOR NF-KAPPA-B BOUND TO DNA/

Citation
Fe. Chen et al., CRYSTAL-STRUCTURE OF P50 P65 HETERODIMER OF TRANSCRIPTION FACTOR NF-KAPPA-B BOUND TO DNA/, Nature, 391(6665), 1998, pp. 410-413
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Multidisciplinary Sciences
Journal title
NatureACNP
ISSN journal
0028-0836
Volume
391
Issue
6665
Year of publication
1998
Pages
410 - 413
Database
ISI
SICI code
0028-0836(1998)391:6665<410:COPPHO>2.0.ZU;2-C
Abstract
The NF-kappa B p50/p65 heterodimer is the classical member of the Rel family of transcription factors which regulate diverse cellular functi ons such as immune response, cell growth, and development(1-3). Other mammalian Rel family members, including the proteins p52, proto-oncopr otein c-Rel, and RelB, all have amino-terminal Rel-homology regions (R HRs)(4-7). The RHR is responsible for the dimerization, DNA binding an d cytosolic localization of these proteins by virtue of complex format ion with inhibitor kappa B proteins(8), Signal-induced removal of kapp a B inhibitors allows translocation of dimers to the cell nucleus and transcriptional regulation of kappa B DNA-containing genes(9), NF-kapp a B specifically recognizes kappa B DNA elements(1,10,11) with a conse nsus sequence of 5'-GGGRNYYYCC-3' (R is an unspecified purine; Y is an unspecified pyrimidine; and N is any nucleotide), Here we report the crystal structure at 2.9 Angstrom resolution of the p50/p65 heterodime r bound to the kappa B DNA of the intronic enhancer of the immunoglobu lin light-chain gene, Our structure reveals a 5-base-pair 5' subsite f or p50, and a 4-base-pair 3' subsite for p65, This structure indicates why the p50/p65 heterodimer interface is stronger than that of either homodimer, A comparison of this structure with those of other Rel dim ers reveals that both subunits adopt variable conformations in a DNA-s equence-dependent manner. Our results explain the different behaviour of the p50/p65 heterodimer with heterologous promoters.