Zinc Fingers PDF

ZINC FINGER protein domains GROUP 1 Abratique | Bugayong | Bunzo | Paz | Tarun VERVIEW 01 02 03 Introduction Structure Functions 04 05 06 Applications Conclusion References INTRODUCTION TRANSCRIPTIONAL FACTORS DOMAINS DNA-BINDING DOMAIN binds to a specific sequence of base pairs in t...

ZINC FINGER protein domains GROUP 1 Abratique | Bugayong | Bunzo | Paz | Tarun VERVIEW 01 02 03 Introduction Structure Functions 04 05 06 Applications Conclusion References INTRODUCTION TRANSCRIPTIONAL FACTORS DOMAINS DNA-BINDING DOMAIN binds to a specific sequence of base pairs in the DNA ACTIVATION DOMAIN regulates transcription by interacting with other proteins INTRODUCTION ZINC FINGERS 01 a repeating motif of ~30 residues within the Xenopus transcription factor TFIIIA 02 used to identify any compact domain stabilized by a Zn ion 03 Employed by many proteins to bind DNA in a sequence-specific manner in order to activate or inhibit particular genes 04 The term finger was derived from the finger-like appearance of the sequences when drawn schematically around a zinc ion. Isalan, 2013 INTRODUCTION Classical Cys2-His2 Finger extremely versatile and found to be present in many transcription factors and in other DNA-binding proteins antiparallel b-hairpin packed against an a-helix A hydrophobic cluster of residues converging from three fixed positions stabilized the classical fingers at the core in addition to chelating zinc consists of tyrosine, phenylalanine, and leucine making this hydrophobic triad highly conserved Klug, 2010 INTRODUCTION IMPORTANCE OF ZINC It maintains the stability of the zinc fingers intracellular proteins are able to stabilize small domains by utilizing metal binding sites Zinc is ideally suited for this purpose as it has a single oxidation state, a fixed and distinguishable ionic radius, and can accommodate both nitrogen and sulfur ligands STRUCTURE BTB DOMAIN has an amphipathic secondary structure that participates in protein-protein interaction, especially self-binding and mediated oligomerization SCAN DOMAIN KRAB DOMAIN Its structural domain is involved primarily with the methylation of substrates engaged in multiple cellular functions including the transcription repression, cytoskeleton dynamics, tetramerization and gating of ion channels, and targeting proteins for ubiquitination SET DOMAIN the KZFPs mainly inhibit transposable elements (TEs) by recruiting transcriptional regulators and heterochromatin formation and DNA methylation in embryonic stem (ES) cells FUNCTIONS Interactions with DNA and RNA Transcriptional control Regulate as transcription factors binds to the promoter region Transcription enhancer/inhibitor Post transcriptional regulation Genome engineering RNA binding properties cleave a chosen genomic sequence and provokes cellular repair Post transcriptional processes mRNA splicing and degradation Zinc finger nucleases Non homologous end joining Small deletions which lead to gene knockout Homology based Gene correction/ addition FUNCTIONS Non-Nucleic acid interactions Protein interactions Lipid binding Other cellular processes striated muscle RING zinc finger protein FYVE zinc finger family interact with DNA, RNA, PAR (poly-ADP-ribose) Cell cycle regulation SMT3b Interact with ubiquitine like protein bind to phosphatidylinositol 3-phosphate (PI3P) mediate further recruitment of a range of proteins ubiquitin-mediated protein degradation, signal transduction, actin targeting, DNA repair, and cell migration APPLICATIONS 1 PHYSIOLOGICAL ROLE 2 TARGETED GENE THERAPY 3 AGRICULTURAL BIOTECHNOLOGY cell proliferation, differentiation, apoptosis, keratinocyte differentiation, intestinal epithelium biology, muscle differentiation, and adipogenesis alterations in ZNFs result in the development of several of diseases specific disease-based therapies: HIV, hemophilia, and cancer oncogenic function: serve as recruiters of chromatin modifiers or as structural proteins that regulate cancer cell migration and invasion increase in yield, disease resistance, or enhanced nutritional content targeted integration in maize, tobacco, and induced pluripotent stem cells REFERENCES Berg, J. 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Li, X., Han, M., Zhang, H., Liu, F., Pan, Y., Zhu, J., Liao, Z., Chen, X., & Zhang, B. (2022). Structures and biological functions of zinc finger proteins and their roles in hepatocellular carcinoma. Biomark Res 10, 2. https://doi.org/10.1186/s40364-021-00345-1 Mackay, J. P., & Crossley, M. (1998). Zinc fingers are sticking together. Trends in biochemical sciences, 23(1), 1-4. Pabo, C. O., Peisach, E., & Grant, R. A. (2001). Design and selection of novel Cys2His2 zinc finger proteins. Annual review of biochemistry, 70(1), 313-340. Urnov, F., Rebar, E., Holmes, M., Zhang, S., & Gregory, P. (2010). Genome editing with engineered zinc finger nucleases. Nat Rev Genet 11, 636–646. https://doi.org/10.1038/nrg2842