The crystal structure analysis of the NarL protein provides afirst look at interactions betweenreceiver and effector domains of a full-length bacterial responseregulator. The N-terminal receiver domain,with 131 amino acids, is folded into a 5-strand
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sheet flanked by 5
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helices, as seen in CheY and in theN-terminal domain of NTRC. The C-terminal DNA-binding domain, with62 amino acids, is a compactbundle of 4
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helices, of which the middle 2 form ahelix-turn-helix motif closely related to that of
Drosophila paired protein and other H-T-HDNA-binding proteins. The 2 domains are connected byan
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helix of 10 amino acids and a 13-residue flexible tether that isnot visible and presumably disorderedin the X-ray structure. In this unphosphorylated form of NarL, theC-terminal domain is turned againstthe receiver domain in a manner that would preclude DNA binding.Activation of NarL via phosphorylationof Asp59 must involve transfer of information to the interdomaininterface and either rotation ordisplacement of the DNA-binding C-terminal domain. Docking of aB-DNA duplex against the isolatedC-terminal domain in the manner observed in
paired proteinand other H-T-H proteins suggests astereochemical basis for DNA sequence preference: T-R-C-C-Y (highaffinity) or T-R-C-T-N (low affinity),which is close to the experimentally observed consensus sequence:T-A-C-Y-N. The NarL structure isa model for other members of the FixJ or LuxR family of bacterialtranscriptional activators, and possiblyto the more distant OmpR and NtrC families as well.