2oen

From Proteopedia

Revision as of 13:28, 23 January 2008

Structural mechanism for the fine-tuning of CcpA function by the small molecule effectors glucose-6-phosphate and fructose-1,6-bisphosphate

Overview

In Gram-positive bacteria, carbon catabolite regulation (CCR) is mediated, by the carbon catabolite control protein A (CcpA), a member of the, LacI-GalR family of transcription regulators. Unlike other LacI-GalR, proteins, CcpA is activated to bind DNA by binding the phosphoproteins, HPr-Ser46-P or Crh-Ser46-P. However, fine regulation of CCR is, accomplished by the small molecule effectors, glucose 6-phosphate (G6P), and fructose 1,6-bisphosphate (FBP), which somehow enhance, CcpA-(HPr-Ser46-P) binding to DNA. Unlike the CcpA-(HPr-Ser46-P) complex, DNA binding by CcpA-(Crh-Ser46-P) is not stimulated by G6P or FBP. To, understand the fine-tuning mechanism of these effectors, we solved the, structures of the CcpA core, DeltaCcpA, which lacks the N-terminal, DNA-binding domain, in complex with HPr-Ser46-P and G6P or FBP. G6P and, FBP bind in a deep cleft, between the N and C subdomains of CcpA. Neither, interacts with HPr-Ser46-P. This suggests that one role of the adjunct, corepressors is to buttress the DNA-binding conformation effected by the, binding of HPr-Ser46-P to the CcpA dimer N subdomains. However, the, structures reveal that an unexpected function of adjunct corepressor, binding is to bolster cross interactions between HPr-Ser46-P residue Arg17, and residues Asp69 and Asp99 of the other CcpA subunit. These cross, contacts, which are weak or not present in the CcpA-(Crh-Ser46-P) complex, stimulate the CcpA-(HPr-Ser46-P)-DNA interaction specifically. Thus, stabilization of the closed conformation and bolstering of cross contacts, between CcpA and its other corepressor, HPr-Ser46-P, provide a molecular, explanation for how adjunct corepressors G6P and FBP enhance the, interaction between CcpA-(HPr-Ser46-P) and cognate DNA.

About this Structure

2OEN is a Protein complex structure of sequences from Bacillus megaterium. Full crystallographic information is available from OCA.

Reference

Structural Mechanism for the Fine-tuning of CcpA Function by The Small Molecule Effectors Glucose 6-Phosphate and Fructose 1,6-Bisphosphate., Schumacher MA, Seidel G, Hillen W, Brennan RG, J Mol Biol. 2007 May 11;368(4):1042-50. Epub 2007 Feb 27. PMID:17376479

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