Structural basis for recognition of S-adenosylhomocysteine by riboswitches

Journal Article · Mon Nov 01 00:00:00 EDT 2010 · RNA

DOI:https://doi.org/10.1261/rna.2341610· OSTI ID:1014334

Edwards, A L; Heroux, A; Reyes, F E; Batey, R T

S-adenosyl-(L)-homocysteine (SAH) riboswitches are regulatory elements found in bacterial mRNAs that up-regulate genes involved in the S-adenosyl-(L)-methionine (SAM) regeneration cycle. To understand the structural basis of SAH-dependent regulation by RNA, we have solved the structure of its metabolite-binding domain in complex with SAH. This structure reveals an unusual pseudoknot topology that creates a shallow groove on the surface of the RNA that binds SAH primarily through interactions with the adenine ring and methionine main chain atoms and discriminates against SAM through a steric mechanism. Chemical probing and calorimetric analysis indicate that the unliganded RNA can access bound-like conformations that are significantly stabilized by SAH to direct folding of the downstream regulatory switch. Strikingly, we find that metabolites bearing an adenine ring, including ATP, bind this aptamer with sufficiently high affinity such that normal intracellular concentrations of these compounds may influence regulation of the riboswitch.

• Research Organization: Brookhaven National Lab. (BNL), Upton, NY (United States)
• Sponsoring Organization: DOE - OFFICE OF SCIENCE
• DOE Contract Number: DE-AC02-98CH10886
• OSTI ID: 1014334
• Report Number(s): BNL-94514-2010-JA; R&D Project: BO-070; KP1605010; TRN: US201111%%287
• Journal Information: RNA, Vol. 16, Issue 11; ISSN 1355-8382
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE
ADENINES
AFFINITY
ATOMS
BEARINGS
CHAINS
GENES
METABOLITES
METHIONINE
REGENERATION
REGULATIONS
RNA
TOPOLOGY
riboswitch
S-adenosylhomocysteine
X-ray crystallography
isothermal titration calorimetry
chemical probing