Structural and dynamic basis for low-affinity, high-selectivity binding of L-glutamine by the glutamine riboswitch Journal Article

   

Authors:	Ren, A.; Xue, Y.; Peselis, A.; Serganov, A.; Al-Hashimi, H. M.; Patel, D. J.
Article Title:	Structural and dynamic basis for low-affinity, high-selectivity binding of L-glutamine by the glutamine riboswitch
Abstract:	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 Mg2+-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 Mg2+ 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.
Keywords:	recognition; glycine riboswitch; lysine riboswitch; gene-expression; crystal-structure; messenger-rna element; nmr; bacteria; ligand-binding; atomic-resolution
Journal Title:	Cell Reports
Volume:	13
Issue:	9
ISSN:	2211-1247
Publisher:	Cell Press
Date Published:	2015-12-01
Start Page:	1800
End Page:	1813
Language:	English
ACCESSION:	WOS:000366047000009
DOI:	10.1016/j.celrep.2015.10.062
PROVIDER:	wos
PMCID:	PMC4690532
PUBMED:	26655897
Notes:	Article -- Source: Wos

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