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2beo
From Proteopedia
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| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 17:35:44 2007'' |
Revision as of 15:30, 5 November 2007
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PRFA, TRANSCRIPTIONAL REGULATOR IN LISTERIA 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
2BEO is a Single protein structure of sequence from Listeria monocytogenes with CL, GLN, PG4 and ACM as ligands. Structure known Active Site: AC1. 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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