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Title: Structural basis for guanidine sensing by the ykkC family of riboswitches

Journal Article · · RNA

Regulation of gene expression by cis-encoded riboswitches is a prevalent theme in bacteria. Of the hundreds of riboswitch families identified, the majority of them remain as orphans, without a clear ligand assignment. The ykkC orphan family was recently characterized as guanidine-sensing riboswitches. In this work, we present a 2.3 Å crystal structure of the guanidine-bound ykkC riboswitch from Dickeya dadantii. The riboswitch folds into a boot-shaped structure, with a coaxially stacked P1/P2 stem forming the boot, and a 3'-P3 stem–loop forming the heel. Sophisticated base-pairing and cross-helix tertiary contacts give rise to the ligand-binding pocket between the boot and the heel. The guanidine is recognized in its positively charged guanidinium form, in its sp2 hybridization state, through a network of coplanar hydrogen bonds and by a cation–π stacking contact on top of a conserved guanosine residue. Disruption of these contacts resulted in severe guanidinium-binding defects. These results provide the structural basis for specific guanidine sensing by ykkC riboswitches and pave the way for a deeper understanding of guanidine detoxification—a previously unappreciated aspect of bacterial physiology.

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:
AC02-06CH11357; R41 GM103403; S10 RR029205
OSTI ID:
1430300
Journal Information:
RNA, Vol. 23, Issue 4; ISSN 1355-8382
Publisher:
Cambridge University PressCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 35 works
Citation information provided by
Web of Science

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Cited By (9)

Structures of two aptamers with differing ligand specificity reveal ruggedness in the functional landscape of RNA journal June 2018
Tandem riboswitches form a natural Boolean logic gate to control purine metabolism in bacteria journal March 2018
Riboswitch diversity and distribution journal April 2017
Acting in tandem journal April 2018
Structure-guided design of a high-affinity ligand for a riboswitch journal January 2019
Guanidine Riboswitch-Regulated Efflux Transporters Protect Bacteria against Ionic Liquid Toxicity journal April 2019
Guanidinium export is the primal function of SMR family transporters journal March 2018
Structural basis for 2′-deoxyguanosine recognition by the 2′-dG-II class of riboswitches journal October 2019
Riboswitches for the alarmone ppGpp expand the collection of RNA-based signaling systems journal May 2018