4ov7 | pdb_00004ov7

Ancestral Steroid Receptor 2 DBD helix mutant - SRE DNA complex

spinqualitylabelsall models 4ov7, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ov7 is a 8 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ZN Related: 4ond, 4oln, 4oor Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Complex gene regulatory networks require transcription factors (TFs) to bind distinct DNA sequences. To understand how novel TF specificity evolves, we combined phylogenetic, biochemical, and biophysical approaches to interrogate how DNA recognition diversified in the steroid hormone receptor (SR) family. After duplication of the ancestral SR, three mutations in one copy radically weakened binding to the ancestral estrogen response element (ERE) and improved binding to a new set of DNA sequences (steroid response elements, SREs). They did so by establishing unfavorable interactions with ERE and abolishing unfavorable interactions with SRE; also required were numerous permissive substitutions, which nonspecifically improved cooperativity and affinity of DNA binding. Our findings indicate that negative determinants of binding play key roles in TFs' DNA selectivity and-with our prior work on the evolution of SR ligand specificity during the same interval-show how a specific new gene regulatory module evolved without interfering with the integrity of the ancestral module. Evolution of DNA specificity in a transcription factor family produced a new gene regulatory module.,McKeown AN, Bridgham JT, Anderson DW, Murphy MN, Ortlund EA, Thornton JW Cell. 2014 Sep 25;159(1):58-68. doi: 10.1016/j.cell.2014.09.003. PMID:25259920 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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