Zinc Fingers 10 and 11 of Miz-1 undergo conformational exchange to achieve specific DNA binding
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Updated: Oct 8, 2025

Direct Protein Delivery to Mammalian Cells Using Cell-permeable Cys2-His2 Zinc-finger Domains
Published on: March 25, 2015
Olivier Boisvert1, Danny Létourneau1, Patrick Delattre1
1Département de biochimie et de génomique fonctionnelle, Institut de Pharmacologie de Sherbrooke and PROTÉO, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, 3001 12 Avenue N, Sherbrooke, Quebec J1H 5N4, Canada.
Abstract:
Miz-1 (ZBTB17) is a poly-zinc finger BTB/POZ transcription factor with 12 consecutive C2H2 zinc fingers (ZFs) that binds transcriptional start sites (TSSs) to regulate the expression of genes involved in cell development and proliferation. As of now, it is not known which of the 12 consecutive ZFs are responsible for the recognition of the 24 base pair consensus sequence found at these TSSs. Evidence suggests ZFs 7-12 plays this role. We provide validation for this and describe the structural and dynamical characterization of unprecedented conformational exchange in the linker between ZFs 10 and 11. This conformational exchange uncouples ZFs 7-10 from 11 and 12 and promotes a scanning-recognition mechanism through which the two segments cooperate to bind two sub-sites at both ends of the consensus. We further show that this can result in the coiling of TSSs as part of Miz-1's mechanism of transcriptional transactivation.
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