SNAP output for PDB entry 5ddo [SNAP web server]

PDB-id

5ddo; SNAP-derived features in text and JSON formats; DNAproDB

Class

RNA binding protein-RNA

Method

X-ray (3.1 Å)

Summary

Structural and dynamic basis for low affinity-high selectivity binding of l-glutamine by the gln-riboswitch

Reference

Ren A, Xue Y, Peselis A, Serganov A, Al-Hashimi HM, Patel DJ (2015): "Structural and Dynamic Basis for Low-Affinity, High-Selectivity Binding of L-Glutamine by the Glutamine Riboswitch." Cell Rep, 13, 1800-1813. doi: 10.1016/j.celrep.2015.10.062.

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 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.