3HS2

Crystal structure of PHD truncated to residue 57 in an orthorhombic space group

Summary for 3HS2

• Entry DOI: 10.2210/pdb3hs2/pdb
• Related: 3DD7 3HRY
• Descriptor: Prevent host death protein, SULFATE ION (3 entities in total)
• Functional Keywords: prevent host death, phd, intrinsic disorder, doc, toxin-antitoxin, antitoxin
• Biological source: Enterobacteria phage P1 (Bacteriophage P1)
• Total number of polymer chains: 8
• Total formula weight: 51729.52

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 (2.2 Å)