Crystal structure of the ankyrin repeat domain of Bcl-3: a unique member of the IkappaB protein family.
IkappaB proteins associate with the transcription factor NF-kappaB via their ankyrin repeat domain. Bcl-3 is an unusual IkappaB protein because it is primarily nucleoplasmic and can lead to enhanced NF-kappaB-dependent transcription, unlike the prototypical IkappaB protein IkappaBalpha, which inhibits NF-kappaB activity by retaining it in the cytoplasm. Here we report the 1.9 A crystal structure of the ankyrin repeat domain of human Bcl-3 and compare it with that of IkappaBalpha bound to NF-kappaB. The two structures are highly similar over the central ankyrin repeats but differ in the N-terminal repeat and at the C-terminus, where Bcl-3 contains a seventh repeat in place of the acidic PEST region of IkappaBalpha. Differences between the two structures suggest why Bcl-3 differs from IkappaBalpha in selectivity towards various NF-kappaB species, why Bcl-3 but not IkappaBalpha can associate with its NF-kappaB partner bound to DNA, and why two molecules of Bcl-3 but only one of IkappaBalpha can bind to its NF-kappaB partner. Comparison of the two structures thus provides an insight into the functional diversity of IkappaB proteins.
Michel
F
F
European Molecular Biology Laboratory, Grenoble Outstation BP 181, 38042 Grenoble, Cedex 9, France.
Soler-Lopez
M
M
Petosa
C
C
Cramer
P
P
Siebenlist
U
U
Müller
C W
CW
D000595:Amino Acid Sequence; D017487:Ankyrins / Q000737:chemistry*; D000081242:B-Cell Lymphoma 3 Protein; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry; D006801:Humans; D020672:I-kappa B Proteins; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry*; D020449:Repetitive Sequences, Amino Acid; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors
D017487:Ankyrins; D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D000072000:NF-KappaB Inhibitor alpha