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2beo

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[[Image:2beo.gif|left|200px]]
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{{STRUCTURE_2beo| PDB=2beo | SCENE= }}
{{STRUCTURE_2beo| PDB=2beo | SCENE= }}
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'''PRFA, TRANSCRIPTIONAL REGULATOR IN LISTERIA MONOCYTOGENES'''
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===PRFA, TRANSCRIPTIONAL REGULATOR IN LISTERIA MONOCYTOGENES===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_15813735}}
==About this Structure==
==About this Structure==
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[[Category: Transcriptional regulator]]
[[Category: Transcriptional regulator]]
[[Category: Virulence]]
[[Category: Virulence]]
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Revision as of 21:37, 27 July 2008

Template:STRUCTURE 2beo

PRFA, TRANSCRIPTIONAL REGULATOR IN LISTERIA MONOCYTOGENES

Template:ABSTRACT PUBMED 15813735

About this Structure

2BEO 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

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