Coenzyme Recognition and Gene Regulation by a Flavin Mononucleotide Riboswitch

Journal Article · Thu Jan 01 00:00:00 EST 2009 · Nature

DOI:https://doi.org/10.1038/nature07642· OSTI ID:980068

Serganov, A; Huang, L; Patel, D

The biosynthesis of several protein cofactors is subject to feedback regulation by riboswitches. Flavin mononucleotide (FMN)-specific riboswitches also known as RFN elements, direct expression of bacterial genes involved in the biosynthesis and transport of riboflavin (vitamin B2) and related compounds. Here we present the crystal structures of the Fusobacterium nucleatum riboswitch bound to FMN, riboflavin and antibiotic roseoflavin. The FMN riboswitch structure, centred on an FMN-bound six-stem junction, does not fold by collinear stacking of adjacent helices, typical for folding of large RNAs. Rather, it adopts a butterfly-like scaffold, stapled together by opposingly directed but nearly identically folded peripheral domains. FMN is positioned asymmetrically within the junctional site and is specifically bound to RNA through interactions with the isoalloxazine ring chromophore and direct and Mg{sup 2+}-mediated contacts with the phosphate moiety. Our structural data, complemented by binding and footprinting experiments, imply a largely pre-folded tertiary RNA architecture and FMN recognition mediated by conformational transitions within the junctional binding pocket. The inherent plasticity of the FMN-binding pocket and the availability of large openings make the riboswitch an attractive target for structure-based design of FMN-like antimicrobial compounds. Our studies also explain the effects of spontaneous and antibiotic-induced deregulatory mutations and provided molecular insights into FMN-based control of gene expression in normal and riboflavin-overproducing bacterial strains.

• Research Organization: Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: DE-AC02-98CH10886
• OSTI ID: 980068
• Report Number(s): BNL-92986-2010-JA; TRN: US201015%%1453
• Journal Information: Nature, Vol. 458
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE
ANTIBIOTICS
ARCHITECTURE
AVAILABILITY
BIOSYNTHESIS
COENZYMES
CONTROL
CRYSTAL STRUCTURE
DATA
DESIGN
ELEMENTS
FEEDBACK
GENE REGULATION
GENES
INTERACTIONS
ISOALLOXAZINES
MUTATIONS
OPENINGS
PHOSPHATES
PLASTICITY
PROTEINS
REGULATIONS
RIBOFLAVIN
RINGS
RNA
STRAINS
TARGETS
TRANSPORT
national synchrotron light source