3HRY

Crystal structure of PHD in a trigonal space group and partially disordered

Summary for 3HRY

• Entry DOI: 10.2210/pdb3hry/pdb
• Related: 3DD7 3HS2
• Descriptor: Prevent host death protein (2 entities in total)
• Functional Keywords: phd, prevent host death, intrinsic disorder, doc, antitoxin
• Biological source: Escherichia coli
• Total number of polymer chains: 3
• Total formula weight: 24429.23

Authors

Garcia-Pino, A.,Loris, R. (deposition date: 2009-06-10, release date: 2010-06-23, Last modification date: 2023-09-06)

Primary citation

Garcia-Pino, A.,Balasubramanian, S.,Wyns, L.,Gazit, E.,De Greve, H.,Magnuson, R.D.,Charlier, D.,van Nuland, N.A.,Loris, R.
Allostery and intrinsic disorder mediate transcription regulation by conditional cooperativity.
Cell(Cambridge,Mass.), 142:101-111, 2010

PubMed Abstract: Regulation of the phd/doc toxin-antitoxin operon involves the toxin Doc as co- or derepressor depending on the ratio between Phd and Doc, a phenomenon known as conditional cooperativity. The mechanism underlying this observed behavior is not understood. Here we show that monomeric Doc engages two Phd dimers on two unrelated binding sites. The binding of Doc to the intrinsically disordered C-terminal domain of Phd structures its N-terminal DNA-binding domain, illustrating allosteric coupling between highly disordered and highly unstable domains. This allosteric effect also couples Doc neutralization to the conditional regulation of transcription. In this way, higher levels of Doc tighten repression up to a point where the accumulation of toxin triggers the production of Phd to counteract its action. Our experiments provide the basis for understanding the mechanism of conditional cooperative regulation of transcription typical of toxin-antitoxin modules. This model may be applicable for the regulation of other biological systems.

PubMed: 20603017
DOI: 10.1016/j.cell.2010.05.039

Experimental method

X-RAY DIFFRACTION (2.25 Å)