7mc3
From Proteopedia
Solution structure of Miz-1 zinc finger 12
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 PubMedMiz-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. Zinc Fingers 10 and 11 of Miz-1 undergo conformational exchange to achieve specific DNA binding.,Boisvert O, Letourneau D, Delattre P, Tremblay C, Jolibois E, Montagne M, Lavigne P Structure. 2022 Apr 7;30(4):623-636.e5. doi: 10.1016/j.str.2021.12.001. Epub 2021, Dec 27. PMID:34963061[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
