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

Ren, Aiming; Wang, Xin  C.; Kellenberger, Colleen  A.; Rajashankar, Kanagalaghatta  R.; Jones, Roger  A.; Hammond, Ming  C.; Patel, Dinshaw  J.

doi:10.1016/j.celrep.2015.03.004

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

Journal Article · Tue Apr 07 00:00:00 EDT 2015 · Cell Reports

DOI:https://doi.org/10.1016/j.celrep.2015.03.004· OSTI ID:1178128

Ren, Aiming ^[1]; Wang, Xin C. ^[2]; Kellenberger, Colleen A. ^[2]; Rajashankar, Kanagalaghatta R. ^[3]; Jones, Roger A. ^[4]; Hammond, Ming C. ^[2]; Patel, Dinshaw J. ^[1]

Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)
Univ. of California, Berkeley, CA (United States). Dept. of Chemistry and Molecular and Cell Biology
Argonne National Lab., IL (US). Advanced Photon Source
State Univ. of New Jersey, Piscataway, NJ (United States). Dept. of Chemistry and Chemical Biology

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.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1178128

Journal Information:: Cell Reports, Journal Name: Cell Reports Journal Issue: 1 Vol. 11; ISSN 2211-1247

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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