The Arthropoda-specific Tramtrack group BTB protein domains use previously unknown interface to form hexamers
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Abstract
BTB (bric-a-brack, Tramtrack, and broad complex) is a diverse group of protein-protein interaction domains found within metazoan proteins. Transcription factors contain a dimerizing BTB subtype with a characteristic N-terminal extension. The Tramtrack group (TTK) is a distinct type of BTB domain, which can multimerize. Single-particle cryo-EM microscopy revealed that the TTK-type BTB domains assemble into a hexameric structure consisting of three canonical BTB dimers connected through a previously uncharacterized interface. We demonstrated that the TTK-type BTB domains are found only in Arthropods and have undergone lineage-specific expansion in modern insects. The Drosophila genome encodes 24 transcription factors with TTK-type BTB domains, whereas only four have non-TTK-type BTB domains. Yeast two-hybrid analysis revealed that the TTK-type BTB domains have an unusually broad potential for heteromeric associations presumably through a dimer-dimer interaction interface. Thus, the TTK-type BTB domains are a structurally and functionally distinct group of protein domains specific to Arthropodan transcription factors.
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“Recently another subclass of multimer-forming human ZBTBs was described ( Mance et al., 2024 ; Park et al., 2024 ).”
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- Authors
- Bonchuk, A. N., Balagurov, K. I., Baradaran, R., Boyko, K. M., Sluchanko, N. N., Khrustaleva, A. M., Burtseva, A. D., Arkova, O. V., Khalisova, K. K., Popov, V. O., Naschberger, A., & Georgiev, P. G.
- Affiliations
- Russian Academy of Sciences (RU)
- King Abdullah University of Science and Technology (SA)
- Corresponding author
- Bonchuk, Artem N
- Georgiev, Pavel G
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2024-09-02
- Volume
- 13
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC11426971
- OpenAlex
- W4402133911
- Cited by
- 21
- References
- 8
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 3 · 2023: 1 · 2022: 2
- FWCI
- 2.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Russian Science Foundation (19-74-10099-P, 19-74-30026-Р)
- Ministry of Science and Higher Education of the Russian Federation (075-15-2019-1661)
- KAUST Baseline Grant (BAS/1/1107-01-01)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- BTB domain, protein-protein interaction domains, hexameric assembly, dimer interface, transcription factors, heteromeric protein complexes, Drosophila
- MeSH terms
- Protein Domains, Animals, Arthropods, Drosophila, Transcription Factors, Cryoelectron Microscopy, Two-Hybrid System Techniques, Protein Multimerization
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