posted on 2021-05-04, 19:14authored byTahseen Raza, Nitin Dhaka, David Joseph, Prikshat Dadhwal, Veera Mohana Rao Kakita, Hanudatta S. Atreya, Sulakshana P. Mukherjee
Transcription factors
bind specifically to their target elements
in the genome, eliciting specific gene expression programs. The nuclear
factor-κB (NF-κB) system is a family of proteins comprising
inducible transcription activators, which play a critical role in
inflammation and cancer. The NF-κB members function as dimers
with each monomeric unit binding the κB-DNA. Despite the available
structures of the various NF-κB dimers in complex with the DNA,
the structural features of these dimers in the nucleic acid-free form
are not well-characterized. Using solution NMR spectroscopy, we characterize
the structural features of 73.1 kDa p50 subunit of the NF-κB
homodimer in the DNA-free form and compare it with the κB DNA-bound
form of the protein. The study further reveals that in the nucleic
acid-free form, the two constituent domains of p50, the N-terminal
and the dimerization domains, are structurally independent of each
other. However, in a complex with the κB DNA, both the domains
of p50 act as a single unit. The study also provides insights into
the mechanism of κB DNA recognition by the p50 subunit of NF-κB.