MBB331_Week9-Fall-2011

G zif268 tfiiia zinc finger protein finger 3 helices

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Unformatted text preview: ins have a series of fingers: Cys2-His2 Zn-finger consensus: Cys Cys-X2 to 4-Cys-X3-Phe-X5-Leu-X2-His-X3-His -each finger ~23 amino acids, with linker between fingers usually 7-8 amino acids TRANSCRIPTION FACTOR FAMILIES: Zinc FINGER MOTIFS Zinc FINGER MOTIFS -C-terminal part of each finger forms α -helices that bind DNA, whereas N-terminal part forms a β -sheet Zif268 Zinc FINGER PROTEIN Zif268 Zinc FINGER PROTEIN e.g. -Zif268 TFIIIA Zinc finger protein finger -3 α -helices fit into DNA -3 -helices major groove major -each of 3 fingers has 2 -each amino acids (all Arg except 1 His) that contact Gs in major groove groove -other residues contact -other DNA phosphate backbone Weaver 2002 Molecular Biology Ed. 2 HYDROGEN BONDS BETWEEN λ REPRESSOR & OPERATOR DNA REPRESSOR OL1 OL1 Weaver 2002 Molecular Biology Ed. 2 • • • Cl & Cro are both helix-turn-helix repressors In both CI & Cro, 2 helix-3 amino acids are conserved (neighbouring In helix-3 Gln & Ser) that bond to specific bp in DNA Gln Helix-2 mediates H-bonding with phosphate backbone (for example Gln 33 in λ repressor) but doesn’t control specificity of target Gln TRANSCRIPTION FACTOR FAMILIES: Zinc FINGER MOTIFS Zinc FINGER MOTIFS • Multiple types of Zn fingers Multiple not all involved in DNA binding not • Distinct type (Cys2/Cys2) of Znfinger transcription factor in finger steroid receptors, consensus: steroid Cys-X2-Cys-X13-Cys-X2-Cys Cys-X • binds short palindromes • Cys2/Cys2 fingers are often Cys nonrepetitive nonrepetitive Weaver 2002 Molecular Biology Ed. 2 TRANSCRIPTION FACTOR FAMILIES: STEROID RECEPTORS STEROID RECEPTORS • Steroid receptors: factor family Steroid activated by steroid hormones & share similar response mechanism mechanism • eg. glucocorticoid receptor glucocorticoid binds glucocorticoids & then translocates into nucleus where it binds GRE enhancers associated with inducible genes associated • Unlike other transcription Unlike factors, DNA-binding & activation not independent not though DNA-binding & hormone binding separable binding Weaver 2002 Molecular Biology Ed. 2 • • • STEROIDS STEROIDS Hormones affect growth, tissue Hormones development & body homeostasis homeostasis Steroid hormones enter cell by Steroid simple diffusion & bind receptor in cytoplasm in Steroid receptors not membrane Steroid associated (unlike usual eukaryotic receptors), but are more like bacterial transcriptional repressors such as trp aporepressor: “free floating” molecule whose conformation is changed by binding to a small molecule molecule Lewin Genes VII 2000 Oxford University Press TRANSCRIPTION FACTOR FAMILIES: STEROID RECEPTORS STEROID RECEPTORS • Glucocorticoid & estrogen r...
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