Identification of an atypical interaction site in the BTB domain of the MYC-interacting zinc-finger protein 1

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2021
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Orth, Barbara
Sander, Bodo
Möglich, Andreas
Eilers, Martin
Lorenz, Sonja
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Structure. Cell Press. 2021, 29(11), pp. 1230-1240.e5. ISSN 0969-2126. eISSN 1878-4186. Available under: doi: 10.1016/j.str.2021.06.005
Zusammenfassung

The repurposing of structurally conserved protein domains in different functional contexts is thought to be a driving force in the evolution of complex protein interaction networks. The BTB/POZ domain is such a versatile binding module that occurs over 200 times in the human proteome with diverse protein-specific adaptations. In BTB-zinc-finger transcription factors, the BTB domain drives homo- and heterodimerization as well as interactions with non-BTB-domain-containing proteins. Which mechanisms encode specificity in these interactions at a structural level is incompletely understood. Here, we uncover an atypical peptide-binding site in the BTB domain of the MYC-interacting zinc-finger protein 1 (MIZ1) that arises from local flexibility of the core BTB fold and may provide a target site for MIZ1-directed therapeutic approaches. Intriguingly, the identified binding mode requires the BTB domain to be in a homodimeric state, thus holding opportunities for functional discrimination between homo- and heterodimers of MIZ1 in the cell.

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ISO 690ORTH, Barbara, Bodo SANDER, Andreas MÖGLICH, Kay DIEDERICHS, Martin EILERS, Sonja LORENZ, 2021. Identification of an atypical interaction site in the BTB domain of the MYC-interacting zinc-finger protein 1. In: Structure. Cell Press. 2021, 29(11), pp. 1230-1240.e5. ISSN 0969-2126. eISSN 1878-4186. Available under: doi: 10.1016/j.str.2021.06.005
BibTex
@article{Orth2021-11-04Ident-54181,
  year={2021},
  doi={10.1016/j.str.2021.06.005},
  title={Identification of an atypical interaction site in the BTB domain of the MYC-interacting zinc-finger protein 1},
  number={11},
  volume={29},
  issn={0969-2126},
  journal={Structure},
  pages={1230--1240.e5},
  author={Orth, Barbara and Sander, Bodo and Möglich, Andreas and Diederichs, Kay and Eilers, Martin and Lorenz, Sonja}
}
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