structure of CrgA from Neisseria meningitidis reveals a new octameric assembly state for LysR transcriptional regulators

LysR-type transcriptional regulators (LTTRs) form the largest family of bacterial regulators acting as both auto-repressors and activators of target promoters, controlling operons involved in a wide variety of cellular processes. The LTTR, CrgA, from the human pathogen Neisseria meningitidis, is upr...

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Bibliographic Details
Published in:Nucleic acids research 2009-08, Vol.37 (14), p.4545-4558
Main Authors: Sainsbury, Sarah, Lane, Laura A, Ren, Jingshan, Gilbert, Robert J, Saunders, Nigel J, Robinson, Carol V, Stuart, David I, Owens, Raymond J
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Bacterial Proteins - chemistry
Bacterial Proteins - metabolism
Binding Sites
Crystallography, X-Ray
DNA - chemistry
DNA - metabolism
Mass Spectrometry
Models, Molecular
Molecular Sequence Data
Neisseria meningitidis
Protein Multimerization
Protein Structure, Tertiary
Structural Biology
Transcription Factors - chemistry
Transcription Factors - metabolism
Ultracentrifugation
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Summary:LysR-type transcriptional regulators (LTTRs) form the largest family of bacterial regulators acting as both auto-repressors and activators of target promoters, controlling operons involved in a wide variety of cellular processes. The LTTR, CrgA, from the human pathogen Neisseria meningitidis, is upregulated during bacterial-host cell contact. Here, we report the crystal structures of both regulatory domain and full-length CrgA, the first of a novel subclass of LTTRs that form octameric rings. Non-denaturing mass spectrometry analysis and analytical ultracentrifugation established that the octameric form of CrgA is the predominant species in solution in both the presence and absence of an oligonucleotide encompassing the CrgA-binding sequence. Furthermore, analysis of the isolated CrgA-DNA complex by mass spectrometry showed stabilization of a double octamer species upon DNA binding. Based on the observed structure and the mass spectrometry findings, a model is proposed in which a hexadecameric array of two CrgA oligomers binds to its DNA target site.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkp445