7azx
From Proteopedia
Crystal structure of the MIZ1-BTB-domain in complex with a HUWE1-derived peptide
Structural highlights
FunctionZBT17_HUMAN Plays a critical role in early lymphocyte development, where it is essential to prevent apoptosis in lymphoid precursors, allowing them to survive in response to IL7 and undergo proper lineage commitment (By similarity). Transcription factor that can function as an activator or repressor depending on its binding partners, and by targeting negative regulators of cell cycle progression. Has been shown to bind to the promoters of adenovirus major late protein and cyclin D1 and activate transcription. Required for early embryonic development during gastrulation.[1] [2] [3] Publication Abstract from PubMedThe 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[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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