This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
2nzu
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:2nzu.jpg|left|200px]] | [[Image:2nzu.jpg|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_2nzu", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | + | --> | |
| - | + | {{STRUCTURE_2nzu| PDB=2nzu | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''Structural mechanism for the fine-tuning of CcpA function by the small molecule effectors G6P and FBP''' | '''Structural mechanism for the fine-tuning of CcpA function by the small molecule effectors G6P and FBP''' | ||
| Line 28: | Line 25: | ||
[[Category: Hillen, W.]] | [[Category: Hillen, W.]] | ||
[[Category: Schumacher, M A.]] | [[Category: Schumacher, M A.]] | ||
| - | [[Category: | + | [[Category: Adjunct corepressor]] |
| - | [[Category: | + | [[Category: Ccpa]] |
| - | [[Category: | + | [[Category: Ccr]] |
| - | [[Category: | + | [[Category: Glucose-6-phosphate]] |
| - | [[Category: | + | [[Category: Hpr-ser46-p]] |
| - | [[Category: | + | [[Category: Laci-galr]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 10:07:31 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 07:07, 4 May 2008
Structural mechanism for the fine-tuning of CcpA function by the small molecule effectors G6P and FBP
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
2NZU 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 Page seeded by OCA on Sun May 4 10:07:31 2008
