Download MendeleyThe Cofactor-Induced Pre-Active Conformation in Phob.
Sola, M., Drew, D.L., Blanco, A.G., Gomis-Ruth, F.X., Coll, M.(2006) Acta Crystallogr D Biol Crystallogr 62: 1046
- PubMed: 16929106
- DOI: https://doi.org/10.1107/S0907444906024541
- Primary Citation of Related Structures:
2IYN - PubMed Abstract:
PhoB is an Escherichia coli transcription factor from a two-component signal transduction system that is sensitive to limiting environmental phosphate conditions. It consists of an N-terminal receiver domain (RD) and a C-terminal DNA-binding domain. The protein is activated upon phosphorylation at the RD, an event that depends on Mg(2+) binding. The structure of PhoB RD in complex with Mg(2+) is presented, which shows three protomers in the asymmetric unit that interact across two different surfaces. One association is symmetric and has been described as a non-active dimerization contact; the other involves the alpha4-beta5-alpha5 interface and recalls the contact found in activated PhoB. However, here this last interaction is not perfectly symmetric and helix alpha4, which in the activated molecule undergoes a helical shift, becomes strongly destabilized in one of the interacting monomers. All protomers bind the cation in a similar manner but, interestingly, at the prospective binding site for the phosphate moiety the side chains of either Glu88 (in helix alpha4) or Trp54 alternate and interact with active-site atoms. When Glu88 is inside the cavity, helix alpha4 is arranged similarly to the unliganded wild-type structure. However, if Trp54 is present, the helix loses its contacts with the active-site cavity and vanishes. Accordingly, the presence of Trp54 in the active site induces a flexible state in helix alpha4, potentially allowing a helical shift that phosphorylation would eventually stabilize.
Organizational Affiliation:
Institut de Biologia Molecular de Barcelona, CSIC, Parc Científic de Barcelona, c/ Josep Samitier 1-5, 08028 Barcelona, Spain. msvcri@ibmb.csic.es
