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Publication Abstract from PubMed

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.

Identification of an atypical interaction site in the BTB domain of the MYC-interacting zinc-finger protein 1.,Orth B, Sander B, Moglich A, Diederichs K, Eilers M, Lorenz S Structure. 2021 Jun 22. pii: S0969-2126(21)00209-4. doi:, 10.1016/j.str.2021.06.005. PMID:34186024^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.