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Title: Structural basis for ligand binding to the guanidine-II riboswitch

Journal Article · · RNA

The guanidine-II riboswitch, also known as mini-ykkC, is a conserved mRNA element with more than 800 examples in bacteria. It consists of two stem–loops capped by identical, conserved tetraloops that are separated by a linker region of variable length and sequence. Like the guanidine-I riboswitch, it controls the expression of guanidine carboxylases and SugE-like genes. The guanidine-II riboswitch specifically binds free guanidinium cations and functions as a translationally controlled on-switch. Here we report the structure of a P2 stem–loop from the Pseudomonas aeruginosa guanidine-II riboswitch aptamer bound to guanidine at 1.57 Å resolution. The hairpins dimerize via the conserved tetraloop, which also contains the binding pocket. Two guanidinium molecules bind near the dimerization interface, one in each tetraloop. The guanidinium cation is engaged in extensive hydrogen bonding to the RNA. Contacts include the Hoogsteen face of a guanine base and three nonbridging phosphate oxygens. Cation–π interactions and ionic interactions also stabilize ligand binding. Finally, the guanidine-II riboswitch utilizes the same recognition strategies as the guanidine-I riboswitch while adopting an entirely different and much smaller RNA fold.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
USDOE Office of Science (SC); National Institutes of Health (NIH)
Grant/Contract Number:
T32GM007223; GM022778
OSTI ID:
1430335
Journal Information:
RNA, Vol. 23, Issue 9; ISSN 1355-8382
Publisher:
Cambridge University PressCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 32 works
Citation information provided by
Web of Science

References (11)

Metabolism of Free Guanidine in Bacteria Is Regulated by a Widespread Riboswitch Class journal January 2017
Biochemical Validation of a Second Guanidine Riboswitch Class in Bacteria journal January 2017
Non-Covalent Interactions: Complexes of Guanidinium with DNA and RNA Nucleobases journal September 2013
Identification of 22 candidate structured RNAs in bacteria using the CMfinder comparative genomics pipeline journal July 2007
Structural Basis for Ligand Binding to the Guanidine-I Riboswitch journal January 2017
Structural basis for guanidine sensing by the ykkC family of riboswitches journal January 2017
Arginine Biosynthesis in Escherichia coli : EXPERIMENTAL PERTURBATION AND MATHEMATICAL MODELING journal December 2007
The Cation−π Interaction journal June 2012
Absolute metabolite concentrations and implied enzyme active site occupancy in Escherichia coli journal June 2009
Cation-pi interactions at non-redundant protein-RNA interfaces journal July 2014
Distribution of diaminopropane and acetylspermidine in Enterobacteriaceae journal February 1996

Cited By (8)

Structure and functional reselection of the Mango-III fluorogenic RNA aptamer journal April 2019
Guanidinium export is the primal function of SMR family transporters journal March 2018
Structure and ligand binding of the glutamine-II riboswitch journal June 2019
Guanidine Riboswitch-Regulated Efflux Transporters Protect Bacteria against Ionic Liquid Toxicity journal April 2019
Structure-guided design of a high-affinity ligand for a riboswitch journal January 2019
Acting in tandem journal April 2018
ykkC riboswitches employ an add-on helix to adjust specificity for polyanionic ligands journal August 2018
Responsive self-assembly of tectoRNAs with loop–receptor interactions from the tetrahydrofolate (THF) riboswitch journal May 2019

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