2bgc
From Proteopedia
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[[Image:2bgc.gif|left|200px]] | [[Image:2bgc.gif|left|200px]] | ||
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'''PRFA-G145S, A CONSTITUTIVE ACTIVE MUTANT OF THE TRANSCRIPTIONAL REGULATOR IN L.MONOCYTOGENES''' | '''PRFA-G145S, A CONSTITUTIVE ACTIVE MUTANT OF THE TRANSCRIPTIONAL REGULATOR IN L.MONOCYTOGENES''' | ||
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[[Category: Heinz, D W.]] | [[Category: Heinz, D W.]] | ||
[[Category: Schubert, W D.]] | [[Category: Schubert, W D.]] | ||
- | [[Category: | + | [[Category: Bacterial infection,human pathogen,transcriptional regulator,transcription]] |
- | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 20:14:51 2008'' | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + |
Revision as of 17:14, 3 May 2008
PRFA-G145S, A CONSTITUTIVE ACTIVE MUTANT OF THE TRANSCRIPTIONAL REGULATOR IN L.MONOCYTOGENES
Overview
Listeria monocytogenes, a Gram-positive, facultative intracellular human pathogen, causes systemic infections with high mortality rate. The majority of the known pathogenicity factors of L. monocytogenes is regulated by a single transcription factor, PrfA. Hyperhaemolytic laboratory strains of L. monocytogenes express the constitutively active mutant PrfA(G145S) inducing virulence gene overexpression independent of environmental conditions. PrfA belongs to the Crp/Fnr family of transcription factors generally activated by a small effector, such as cAMP or O(2). We present the crystal structures of wild-type PrfA, the first Gram-positive member of the Crp/Fnr family, and of the constitutively active mutant PrfA(G145S). Cap (Crp) has previously been described exclusively in the cAMP-induced (DNA-free and -bound) conformation. By contrast, the PrfA structures present views both of the non-induced state and of the mutationally activated form. The low DNA-binding affinity of wild-type PrfA is supported both structurally (partly disordered helix-turn-helix motif, overall geometry of the HTH alpha-helices deviates from Cap) and by surface plasmon resonance analyses (K(D) = 0.9 microM). In PrfA(G145S) the HTH motifs dramatically rearrange to adopt a conformation comparable to cAMP-induced Cap and hence favourable for DNA binding, supported by a DNA-binding affinity of 50 nM. Finally, the hypothesis that wild-type PrfA, like other Crp/Fnr family members, may require an as yet unidentified cofactor for activation is supported by the presence of a distinct tunnel in PrfA, located at the interface of the beta-barrel and the DNA-binding domain.
About this Structure
2BGC is a Single protein structure of sequence from Listeria monocytogenes. Full crystallographic information is available from OCA.
Reference
The mutation G145S in PrfA, a key virulence regulator of Listeria monocytogenes, increases DNA-binding affinity by stabilizing the HTH motif., Eiting M, Hageluken G, Schubert WD, Heinz DW, Mol Microbiol. 2005 Apr;56(2):433-46. PMID:15813735 Page seeded by OCA on Sat May 3 20:14:51 2008