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Title: Structural Basis for Molecular Discrimination by a 3',3'-cGAMP Sensing Riboswitch

Cyclic dinucleotides are second messengers that target the adaptor STING and stimulate the innate immune response in mammals. Besides protein receptors, there are bacterial riboswitches that selectively recognize cyclic dinucleotides. We recently discovered a natural riboswitch that targets 3',3'-cGAMP, which is distinguished from the endogenous mammalian signal 2',3'-cGAMP by its backbone connectivity. Here, we report on structures of the aptamer domain of the 3',3'-cGAMP riboswitch from Geobacter in the 3',3'-cGAMP and c-di-GMP bound states. The riboswitch adopts a tuning forklike architecture with a junctional ligand-binding pocket and different orientations of the arms are correlated with the identity of the bound cyclic dinucleotide. Subsequent biochemical experiments revealed that specificity of ligand recognition can be affected by point mutations outside of the binding pocket, which has implications for both the assignment and reengineering of riboswitches in this structural class.
Authors:
 [1] ;  [2] ;  [2] ;  [3] ;  [4] ;  [2] ;  [1]
  1. Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)
  2. Univ. of California, Berkeley, CA (United States). Dept. of Chemistry and Molecular and Cell Biology
  3. Argonne National Lab., IL (US). Advanced Photon Source
  4. State Univ. of New Jersey, Piscataway, NJ (United States). Dept. of Chemistry and Chemical Biology
Publication Date:
OSTI Identifier:
1178128
Grant/Contract Number:
AC02-06CH11357
Type:
Accepted Manuscript
Journal Name:
Cell Reports
Additional Journal Information:
Journal Volume: 11; Journal Issue: 1; Journal ID: ISSN 2211-1247
Publisher:
Elsevier
Research Org:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES