Insights into Strand Exchange in BTB Domain Dimers from the Crystal Structures of FAZF and Miz1

Journal Article · Wed Sep 22 04:00:00 EDT 2010 · J. Mol. Biol.

DOI:https://doi.org/10.1016/j.jmb.2010.05.028· OSTI ID:1002720

Stogios, Peter J; Cuesta-Seijo, Jose Antonio; Chen, Lu; Pomroy, Neil C; Privé, Gilbert G ^[1]

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1. Toronto

The BTB domain is a widely distributed protein-protein interaction motif that is often found at the N-terminus of zinc finger transcription factors. Previous crystal structures of BTB domains have revealed tightly interwound homodimers, with the N-terminus from one chain forming a two-stranded anti-parallel {beta}-sheet with a strand from the other chain. We have solved the crystal structures of the BTB domains from Fanconi anemia zinc finger (FAZF) and Miz1 (Myc-interacting zinc finger 1) to resolutions of 2.0 {angstrom} and 2.6 {angstrom}, respectively. Unlike previous examples of BTB domain structures, the FAZF BTB domain is a nonswapped dimer, with each N-terminal {beta}-strand associated with its own chain. As a result, the dimerization interface in the FAZF BTB domain is about half as large as in the domain-swapped dimers. The Miz1 BTB domain resembles a typical swapped BTB dimer, although it has a shorter N-terminus that is not able to form the interchain sheet. Using cysteine cross-linking, we confirmed that the promyelocytic leukemia zinc finger (PLZF) BTB dimer is strand exchanged in solution, while the FAZF BTB dimer is not. A phylogenic tree of the BTB fold based on both sequence and structural features shows that the common ancestor of the BTB domain in BTB-ZF (bric a brac, tramtrack, broad-complex zinc finger) proteins was a domain-swapped dimer. The differences in the N-termini seen in the FAZF and Miz1 BTB domains appear to be more recent developments in the structural evolution of the domain.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1002720
• Journal Information: J. Mol. Biol., Journal Name: J. Mol. Biol. Journal Issue: (5) ; 07, 2010 Vol. 400; ISSN JMOBAK; ISSN 0022-2836
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
ANEMIAS
CHAINS
CRYSTAL STRUCTURE
CYSTEINE
DIMERIZATION
DIMERS
DOMAIN STRUCTURE
LEUKEMIA
PROTEINS
TRANSCRIPTION FACTORS
ZINC