Structural and Dynamic Basis for Low-Affinity, High-Selectivity Binding of L-Glutamine by the Glutamine Riboswitch.
Published
Journal Article
Naturally occurring L-glutamine riboswitches occur in cyanobacteria and marine metagenomes, where they reside upstream of genes involved in nitrogen metabolism. By combining X-ray, NMR, and MD, we characterized an L-glutamine-dependent conformational transition in the Synechococcus elongatus glutamine riboswitch from tuning fork to L-shaped alignment of stem segments. This transition generates an open ligand-binding pocket with L-glutamine selectivity enforced by Mg(2+)-mediated intermolecular interactions. The transition also stabilizes the P1 helix through a long-range "linchpin" Watson-Crick G-C pair-capping interaction, while melting a short helix below P1 potentially capable of modulating downstream readout. NMR data establish that the ligand-free glutamine riboswitch in Mg(2+) solution exists in a slow equilibrium between flexible tuning fork and a minor conformation, similar, but not identical, to the L-shaped bound conformation. We propose that an open ligand-binding pocket combined with a high conformational penalty for forming the ligand-bound state provide mechanisms for reducing binding affinity while retaining high selectivity.
Full Text
Duke Authors
Cited Authors
- Ren, A; Xue, Y; Peselis, A; Serganov, A; Al-Hashimi, HM; Patel, DJ
Published Date
- December 1, 2015
Published In
Volume / Issue
- 13 / 9
Start / End Page
- 1800 - 1813
PubMed ID
- 26655897
Pubmed Central ID
- 26655897
Electronic International Standard Serial Number (EISSN)
- 2211-1247
Digital Object Identifier (DOI)
- 10.1016/j.celrep.2015.10.062
Language
- eng
Conference Location
- United States