4BDO

Crystal structure of the GluK2 K531A-T779G LBD dimer in complex with kainate

Summary for 4BDO

• Entry DOI: 10.2210/pdb4bdo/pdb
• Related: 1S50 1S7Y 1S9T 1SD3 1TT1 1YAE 2I0B 2I0C 2XXR 2XXT 2XXU 2XXV 2XXW 2XXX 2XXY 4BDL 4BDM 4BDN 4BDQ 4BDR
• Descriptor: GLUTAMATE RECEPTOR, IONOTROPIC KAINATE 2, 3-(CARBOXYMETHYL)-4-ISOPROPENYLPROLINE, SODIUM ION, ... (5 entities in total)
• Functional Keywords: metal transport, ionotropic glutamate receptor, kainate receptor
• Biological source: RATTUS NORVEGICUS (NORWAY RAT)
• Cellular location: Cell membrane; Multi-pass membrane protein: P42260
• Total number of polymer chains: 4
• Total formula weight: 119187.16

Authors

Nayeem, N.,Mayans, O.,Green, T. (deposition date: 2012-10-05, release date: 2013-04-10, Last modification date: 2024-10-23)

Primary citation

Nayeem, N.,Mayans, O.,Green, T.
Correlating Efficacy and Desensitization with Gluk2 Ligand-Binding Domain Movements.
Open Biol., 3:0051-, 2013

PubMed Abstract: Gating of AMPA- and kainate-selective ionotropic glutamate receptors can be defined in terms of ligand affinity, efficacy and the rate and extent of desensitization. Crucial insights into all three elements have come from structural studies of the ligand-binding domain (LBD). In particular, binding-cleft closure is associated with efficacy, whereas dissociation of the dimer formed by neighbouring LBDs is linked with desensitization. We have explored these relationships in the kainate-selective subunit GluK2 by studying the effects of mutating two residues (K531 and R775) that form key contacts within the LBD dimer interface, but whose truncation unexpectedly attenuates desensitization. One mutation (K531A) also switches the relative efficacies of glutamate and kainate. LBD crystal structures incorporating these mutations revealed several conformational changes that together explain their phenotypes. K531 truncation results in new dimer contacts, consistent with slower desensitization and sideways movement in the ligand-binding cleft correlating with efficacy. The tested mutants also disrupted anion binding; no chloride was detected in the dimer-interface site, including in R775A where absence of chloride was the only structural change evident. From this, we propose that the charge balance in the GluK2 LBD dimer interface maintains a degree of instability, necessary for rapid and complete desensitization.

PubMed: 23720540
DOI: 10.1098/RSOB.130051

Experimental method

X-RAY DIFFRACTION (2.55 Å)