Article
- The EMBO Journal (2001) 20, 6180 - 6190
- doi:10.1093/emboj/20.22.6180
Crystal structure of the ankyrin repeat domain of Bcl-3: a unique member of the I
B protein family
Fabrice Michel1, Montserrat Soler-Lopez1, Carlo Petosa1, Patrick Cramer1,2, Ulrich Siebenlist3 and Christoph W. Müller1
- European Molecular Biology Laboratory, Grenoble Outstation BP 181, 38042 Grenoble, Cedex 9, France
- Present address: Institute of Biochemistry, Gene Center, University of Munich, Feodor-Lynen-Strasse 25, D-81377 Munich, Germany
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA
Correspondence to:
Christoph W. Müller, E-mail: mueller@embl-grenoble.fr
Received 20 August 2001; Accepted 27 September 2001; Revised 26 September 2001
Abstract
I
B proteins associate with the transcription factor NF-B via their ankyrin repeat domain. Bcl-3 is an unusual IB protein because it is primarily nucleoplasmic and can lead to enhanced NF-B-dependent transcription, unlike the prototypical IB protein IB
, which inhibits NF-B activity by retaining it in the cytoplasm. Here we report the 1.9 Å crystal structure of the ankyrin repeat domain of human Bcl-3 and compare it with that of IB bound to NF-B. 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 IB. Differences between the two structures suggest why Bcl-3 differs from IB in selectivity towards various NF-B species, why Bcl-3 but not IB can associate with its NF-B partner bound to DNA, and why two molecules of Bcl-3 but only one of IB can bind to its NF-B partner. Comparison of the two structures thus provides an insight into the functional diversity of IB proteins.
Keywords:
- Bcl-3,
- IB proteins,
- NF-B transcription factors
