The cofactor-induced pre-active conformation in PhoB

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 t...

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Detalles Bibliográficos
Autores: Solà, Maria, Drew, Devin Lee, Blanco, Alexandre G., Gomis-Rüth, F. Xavier, Coll, Miquel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2006
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/107603
Acceso en línea:http://hdl.handle.net/10261/107603
Access Level:acceso abierto
Palabra clave:Tryptophan
PhoB protein, Bacteria
Metal
Bacterial proteins
Cation
Magnesium
Descripción
Sumario: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 Mg2+ binding. The structure of PhoB RD in complex with Mg2+ 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 α4-β5-α5 interface and recalls the contact found in activated PhoB. However, here this last interaction is not perfectly symmetric and helix α4, 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 α4) or Trp54 alternate and interact with active-site atoms. When Glu88 is inside the cavity, helix α4 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 α4, potentially allowing a helical shift that phosphorylation would eventually stabilize. © 2006 International Union of Crystallography - all rights reserved.