Structure of the Escherichia coli Leucine-responsive Regulatory Protein Lrp Reveals a Novel Octameric Assembly

• Published in: Journal of molecular biology Vol. 366; no. 5; pp. 1589 - 1602
• Main Authors: de los Rios, Stephanie, Perona, John J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 09.03.2007
• Subjects: Amino Acid Sequence; BASIC BIOLOGICAL SCIENCES; Binding Sites; CRYSTALLIZATION; Crystallography, X-Ray; Dimerization; DIMERS; DNA; DNA - isolation & purification; DNA - metabolism; ESCHERICHIA COLI; Escherichia coli - genetics; Escherichia coli - growth & development; Escherichia coli - metabolism; Gene Deletion; Gene Expression Regulation, Bacterial; Hydrogen Bonding; LEUCINE; Leucine - genetics; Leucine - metabolism; Leucine-Responsive Regulatory Protein - chemistry; Leucine-Responsive Regulatory Protein - genetics; Leucine-Responsive Regulatory Protein - isolation & purification; Leucine-Responsive Regulatory Protein - metabolism; Models, Molecular; Molecular Sequence Data; Mutagenesis; Operon; ORIENTATION; Other,OTHER; pap operon; Protein Binding; Protein Structure, Quaternary; Protein Structure, Tertiary; PROTEINS; protein–DNA interactions; Sequence Homology, Amino Acid; Spectrometry, Mass, Electrospray Ionization; Spectrum Analysis, Raman; Static Electricity; SYMMETRY; Transcription, Genetic; transcriptional regulation; X-Ray Diffraction; pap operon; protein–DNA interactions; HTH; transcriptional regulation; SAM; RAM
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2006.12.032

The structure of Escherichia coli leucine-responsive regulatory protein (Lrp) co-crystallized with a short duplex oligodeoxynucleotide reveals a novel quaternary assembly in which the protein octamer forms an open, linear array of four dimers. In contrast, structures of the Lrp homologs LrpA, LrpC and AsnC crystallized in the absence of DNA show that these proteins instead form highly symmetrical octamers in which the four dimers form a closed ring. Although the DNA is disordered within the Lrp crystal, comparative analyses suggest that the observed differences in quaternary state may arise from DNA interactions during crystallization. Interconversion of these conformations, possibly in response to DNA or leucine binding, provides an underlying mechanism to alter the relative spatial orientation of the DNA-binding domains. Breaking of the closed octamer symmetry may be a common essential step in the formation of active DNA complexes by all members of the Lrp/AsnC family of transcriptional regulatory proteins.