2HAP

STRUCTURE OF A HAP1-18/DNA COMPLEX REVEALS THAT PROTEIN/DNA INTERACTIONS CAN HAVE DIRECT ALLOSTERIC EFFECTS ON TRANSCRIPTIONAL ACTIVATION

Summary for 2HAP

• Entry DOI: 10.2210/pdb2hap/pdb
• Descriptor: DNA (5'-D(*AP*CP*GP*CP*TP*AP*TP*TP*AP*TP*CP*GP*CP*TP*AP*TP*TP*AP*GP*T)-3'), DNA (5'-D(*AP*CP*TP*AP*AP*TP*AP*GP*CP*GP*AP*TP*AP*AP*TP*AP*GP*CP*GP*T)-3'), PROTEIN (HEME ACTIVATOR PROTEIN), ... (5 entities in total)
• Functional Keywords: complex transcription factor-dna, asymmetry, transcriptional activation, hyperactive mutant, gene regulation-dna complex, gene regulation/dna
• Biological source: Saccharomyces cerevisiae (baker's yeast); More
• Total number of polymer chains: 4
• Total formula weight: 31985.07

Authors

King, D.A.,Zhang, L.,Guarente, L.,Marmorstein, R. (deposition date: 1998-09-17, release date: 1999-11-10, Last modification date: 2024-02-14)

Primary citation

King, D.A.,Zhang, L.,Guarente, L.,Marmorstein, R.
Structure of HAP1-18-DNA implicates direct allosteric effect of protein-DNA interactions on transcriptional activation.
Nat.Struct.Biol., 6:22-27, 1999

PubMed Abstract: HAP1 is a yeast transcriptional activator that binds with equal affinity to the dissimilar upstream activation sequences UAS1 and UAS(CYC7), but activates transcription differentially when bound to each site. HAP1-18 harbors an amino acid change in the DNA binding domain. While binding UAS1 poorly, HAP1-18 binds UAS(CYC7) with wild-type properties and activates transcription at elevated levels relative to HAP1. We have determined the structure of HAP1-18-UAS(CYC7) and have compared it to HAP1-UAS(CYC7). Unexpectedly, the single amino acid substitution in HAP1-18 nucleates a significantly altered hydrogen bond interface between the protein and DNA resulting in DNA conformational changes and an ordering of one N-terminal arm of the protein dimer along the DNA minor groove. These observations, together with a large subset of transcriptionally defective mutations in the HAP1 DNA-binding domain that map to the HAP1-DNA interface, suggest that protein-DNA interactions may have direct allosteric effects on transcriptional activation.

PubMed: 9886287
DOI: 10.1038/4893

Experimental method

X-RAY DIFFRACTION (2.5 Å)