Rigid body essential X-ray crystallography: distinguishing the bend and twist of glutamate receptor ligand binding domains

Proteins
Esben J Bjerrum, Philip C Biggin

Abstract

The ligand-binding domain (LBD) from the ionotropic glutamate receptor subtype 2 (GluR2) has been shown to adopt a range of ligand-dependent conformational states. These states have been described in terms of the rotation required to fit subdomain (lobe) 2 following superposition of subdomain (lobe) 1. The LBD has a closed-cleft conformation for full agonists, but partial agonists induce a range of closure, which in turn controls the open probability of discrete subconductance states in the full-length receptor. Although this description is useful, it may not account for all physiologically important motions that the receptor undergoes. We have used an approach that combines the methods of essential dynamics and rigid-body dynamics to analyze 124 monomer domains from 55 crystal structures of the GluR2 LBD. We are able to show that partial agonists also induce a significant amount of twist that would not be anticipated using one rotational descriptor between apo and full-agonist-bound states. Furthermore, one of the crystal structures (chain B from 1P1U, the GluR2 L650T-AMPA complex), which has been suggested to represent an agonist-bound inactive form of the receptor, lies at the extreme of this twist motion. We suggest that pa...Continue Reading

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Citations

Aug 27, 2013·Neuropharmacology·Trine KvistHans Bräuner-Osborne
Feb 15, 2011·Nature Structural & Molecular Biology·Albert Y Lau, Benoît Roux
Jan 29, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Amanda Birdsey-BensonDean R Madden
Jun 24, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yanina Levchenko-LambertDoris K Patneau
Sep 10, 2009·Neuropharmacology·Pekka A PostilaOlli T Pentikäinen

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