P50
NFkappaB is an important and
ubiquitous transcription factor formed by various homo- and heterodimers of the
NFkappaB family. The active transcription factor regulates genes involved in
immune, inflammatory and survival responses. Specificity in gene regulation is
achieved, at least in part, by the distinct DNA binding preferences of the
various homo- and heterodimers and by the complex pathways that lead to
signal-induced degradation of the IkappaB inhibitors. Analytical
ultracentrifugation and hydrodynamic bead modelling were used to model the
solution structures of the NFkappaB family member p50, its inhibitor
IkappaBgamma and their complex. Sedimentation equilibrium (SE) and
sedimentation velocity (SV) data show that p50 is a dimer in solution with a
sedimentation coefficient consistent with a conformation intermediate between
the closed conformation observed in the crystal structure of the p50
(N-terminal domain)-p65 heterodimer complexed with IkappaBalpha and the open
conformation adopted by p50 when bound to DNA. SE and SV data show that IkappaBgamma
is a monomer in solution and is prone to aggregation over time. p50 forms a 2:1
stoichiometric complex with IkappaBgamma in solution with a sedimentation
coefficient consistent with a closed conformation for the p50 dimer.
PMID: 15043934 [PubMed - in process]