Sibling rivalry among the ZBTB transcription factor family: homodimers versus heterodimers

Piepoli, Sofia and Barakat, Sarah Mohammed Mohammed and Noğay, Liyne and Şimşek, Büşra and Akköse, Ümit and Taşkıran, Hakan and Tolay, Nazife and Gezen, Melike and Yeşilada, Canberk Yarkın and Tuncay, Mustafa and Adebali, Ogün and Atılgan, Canan and Erman, Batu (2022) Sibling rivalry among the ZBTB transcription factor family: homodimers versus heterodimers. Life Science Alliance, 5 (11). ISSN 2575-1077

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The BTB domain is an oligomerization domain found in over 300 proteins encoded in the human genome. In the family of BTB domain and zinc finger–containing (ZBTB) transcription factors, 49 members share the same protein architecture. The N-terminal BTB domain is structurally conserved among the family members and serves as the dimerization site, whereas the C-terminal zinc finger motifs mediate DNA binding. The available BTB domain structures from this family reveal a natural inclination for homodimerization. In this study, we investigated the potential for heterodimer formation in the cellular environment. We selected five BTB homodimers and four heterodimer structures. We performed cell-based binding assays with fluorescent protein–BTB domain fusions to assess dimer formation. We tested the binding of several BTB pairs, and we were able to confirm the heterodimeric physical interaction between the BTB domains of PATZ1 and PATZ2, previously reported only in an interactome mapping experiment. We also found this pair to be co-expressed in several immune system cell types. Finally, we used the available structures of BTB domain dimers and newly constructed models in extended molecular dynamics simulations (500 ns) to understand the energetic determinants of homo- and heterodimer formation. We conclude that heterodimer formation, although frequently described as less preferred than homodimers, is a possible mechanism to increase the combinatorial specificity of this transcription factor family.
Item Type: Article
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Biological Sciences & Bio Eng.
Faculty of Engineering and Natural Sciences
Depositing User: Ogün Adebali
Date Deposited: 23 Mar 2023 11:43
Last Modified: 23 Mar 2023 11:43

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