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Title: Structures of two aptamers with differing ligand specificity reveal ruggedness in the functional landscape of RNA

Abstract

Two classes of riboswitches related to the ykkC guanidine-I riboswitch bind phosphoribosyl pyrophosphate (PRPP) and guanosine tetraphosphate (ppGpp). Here we report the co-crystal structure of the PRPP aptamer and its ligand. We also report the structure of the G96A point mutant that prefers ppGpp over PRPP with a dramatic 40,000-fold switch in specificity. The ends of the aptamer form a helix that is not present in the guanidine aptamer and is involved in the expression platform. In the mutant, the base of ppGpp replaces G96 in three-dimensional space. This disrupts the S-turn, which is a primary structural feature of the ykkC RNA motif. These dramatic differences in ligand specificity are achieved with minimal mutations. ykkC aptamers are therefore a prime example of an RNA fold with a rugged fitness landscape. The ease with which the ykkC aptamer acquires new specificity represents a striking case of evolvability in RNA.

Authors:
ORCiD logo [1];  [1]; ORCiD logo [1]
  1. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
1452850
Resource Type:
Journal Article
Resource Relation:
Journal Name: eLife; Journal Volume: 7; Journal Issue: 2018
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Knappenberger, Andrew John, Reiss, Caroline Wetherington, and Strobel, Scott A. Structures of two aptamers with differing ligand specificity reveal ruggedness in the functional landscape of RNA. United States: N. p., 2018. Web. doi:10.7554/eLife.36381.
Knappenberger, Andrew John, Reiss, Caroline Wetherington, & Strobel, Scott A. Structures of two aptamers with differing ligand specificity reveal ruggedness in the functional landscape of RNA. United States. doi:10.7554/eLife.36381.
Knappenberger, Andrew John, Reiss, Caroline Wetherington, and Strobel, Scott A. Thu . "Structures of two aptamers with differing ligand specificity reveal ruggedness in the functional landscape of RNA". United States. doi:10.7554/eLife.36381.
@article{osti_1452850,
title = {Structures of two aptamers with differing ligand specificity reveal ruggedness in the functional landscape of RNA},
author = {Knappenberger, Andrew John and Reiss, Caroline Wetherington and Strobel, Scott A.},
abstractNote = {Two classes of riboswitches related to the ykkC guanidine-I riboswitch bind phosphoribosyl pyrophosphate (PRPP) and guanosine tetraphosphate (ppGpp). Here we report the co-crystal structure of the PRPP aptamer and its ligand. We also report the structure of the G96A point mutant that prefers ppGpp over PRPP with a dramatic 40,000-fold switch in specificity. The ends of the aptamer form a helix that is not present in the guanidine aptamer and is involved in the expression platform. In the mutant, the base of ppGpp replaces G96 in three-dimensional space. This disrupts the S-turn, which is a primary structural feature of the ykkC RNA motif. These dramatic differences in ligand specificity are achieved with minimal mutations. ykkC aptamers are therefore a prime example of an RNA fold with a rugged fitness landscape. The ease with which the ykkC aptamer acquires new specificity represents a striking case of evolvability in RNA.},
doi = {10.7554/eLife.36381},
journal = {eLife},
number = 2018,
volume = 7,
place = {United States},
year = {Thu Jun 07 00:00:00 EDT 2018},
month = {Thu Jun 07 00:00:00 EDT 2018}
}