2oen: Difference between revisions
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'''Structural mechanism for the fine-tuning of CcpA function by the small molecule effectors glucose-6-phosphate and fructose-1,6-bisphosphate''' | '''Structural mechanism for the fine-tuning of CcpA function by the small molecule effectors glucose-6-phosphate and fructose-1,6-bisphosphate''' | ||
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[[Category: Schumacher, M A.]] | [[Category: Schumacher, M A.]] | ||
[[Category: Seidel, G.]] | [[Category: Seidel, G.]] | ||
[[Category: | [[Category: Adjunct corepressor]] | ||
[[Category: | [[Category: Ccpa]] | ||
[[Category: | [[Category: Ccr]] | ||
[[Category: | [[Category: Crh]] | ||
[[Category: | [[Category: Hpr]] | ||
[[Category: | [[Category: Protein-dna]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:44:57 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 10:44, 4 May 2008
Structural mechanism for the fine-tuning of CcpA function by the small molecule effectors glucose-6-phosphate and fructose-1,6-bisphosphate
OverviewOverview
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 StructureAbout this Structure
2OEN is a Protein complex structure of sequences from Bacillus megaterium. Full crystallographic information is available from OCA.
ReferenceReference
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 Page seeded by OCA on Sun May 4 10:44:57 2008