4OT9

crystal structure of the C-terminal domain of p100/NF-kB2

Summary for 4OT9

• Entry DOI: 10.2210/pdb4ot9/pdb
• Descriptor: Nuclear factor NF-kappa-B p100 subunit, SULFATE ION (2 entities in total)
• Functional Keywords: nf-kb transcription factor, transcription
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q00653
• Total number of polymer chains: 1
• Total formula weight: 38474.31

Authors

Tao, Z.H.,Huang, D.B.,Fusco, A.,Gupta, K.,Ware, C.F.,Duynne, G.V. (deposition date: 2014-02-13, release date: 2015-01-14, Last modification date: 2024-02-28)

Primary citation

Tao, Z.,Fusco, A.,Huang, D.B.,Gupta, K.,Young Kim, D.,Ware, C.F.,Van Duyne, G.D.,Ghosh, G.
p100/I kappa B delta sequesters and inhibits NF-kappa B through kappaBsome formation.
Proc.Natl.Acad.Sci.USA, 111:15946-15951, 2014

PubMed Abstract: Degradation of I kappaB (κB) inhibitors is critical to activation of dimeric transcription factors of the NF-κB family. There are two types of IκB inhibitors: the prototypical IκBs (IκBα, IκBβ, and IκBε), which form low-molecular-weight (MW) IκB:NF-κB complexes that are highly stable, and the precursor IκBs (p105/IκBγ and p100/IκBδ), which form high-MW assemblies, thereby suppressing the activity of nearly half the cellular NF-κB [Savinova OV, Hoffmann A, Ghosh G (2009) Mol Cell 34(5):591-602]. The identity of these larger assemblies and their distinct roles in NF-κB inhibition are unknown. Using the X-ray crystal structure of the C-terminal domain of p100/IκBδ and functional analysis of structure-guided mutants, we show that p100/IκBδ forms high-MW (IκBδ)4:(NF-κB)4 complexes, referred to as kappaBsomes. These IκBδ-centric "kappaBsomes" are distinct from the 2:2 complexes formed by IκBγ. The stability of the IκBδ tetramer is enhanced upon association with NF-κB, and hence the high-MW assembly is essential for NF-κB inhibition. Furthermore, weakening of the IκBδ tetramer impairs both its association with NF-κB subunits and stimulus-dependent processing into p52. The unique ability of p100/IκBδ to stably interact with all NF-κB subunits by forming kappaBsomes demonstrates its importance in sequestering NF-κB subunits and releasing them as dictated by specific stimuli for developmental programs.

PubMed: 25349408
DOI: 10.1073/pnas.1408552111

Experimental method

X-RAY DIFFRACTION (3.35 Å)