First time at Proteopedia? Click on the green links: they change the 3D image. Click and drag the molecules. Proteopedia is a 3D, interactive encyclopedia of proteins, RNA, DNA and other molecules. With a free user account, you can edit pages in Proteopedia. Visit the Main Page to learn more.
3kfm
From Proteopedia
| 3kfm, resolution 2.20Å () | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Ligands: | |||||||||
| Gene: | Glur4, Gria4 (Rattus norvegicus) | ||||||||
| Related: | 3kei | ||||||||
| |||||||||
| |||||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Contents |
Crystal Structure of the GluA4 Ligand-Binding domain L651V mutant in complex with kainate
AMPA receptors (AMPARs) are tetrameric ligand-gated ion channels that couple the energy of glutamate binding to the opening of a transmembrane channel. Crystallographic and electrophysiological analysis of AMPARs has suggested a coupling between (1) cleft closure in the bilobate ligand-binding domain (LBD), (2) the resulting separation of transmembrane helix attachment points across subunit dimers, and (3) agonist efficacy. In general, more efficacious agonists induce greater degrees of cleft closure and transmembrane separation than partial agonists. Several apparent violations of the cleft-closure/efficacy paradigm have emerged, although in all cases, intradimer separation remains as the driving force for channel opening. Here, we examine the structural basis of partial agonism in GluA4 AMPARs. We find that the L651V substitution enhances the relative efficacy of kainate without increasing either LBD cleft closure or transmembrane separation. Instead, the conformational change relative to the wild-type:kainate complex involves a twisting motion with the efficacy contribution opposite from that expected based on previous analyses. As a result, channel opening may involve transmembrane rearrangements with a significant rotational component. Furthermore, a two-dimensional analysis of agonist-induced GluA2 LBD motions suggests that efficacy is not a linearly varying function of lobe 2 displacement vectors, but is rather determined by specific conformational requirements of the transmembrane domains.
Enhanced efficacy without further cleft closure: reevaluating twist as a source of agonist efficacy in AMPA receptors., Birdsey-Benson A, Gill A, Henderson LP, Madden DR, J Neurosci. 2010 Jan 27;30(4):1463-70. PMID:20107073
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
3kfm is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
See Also
Reference
- Birdsey-Benson A, Gill A, Henderson LP, Madden DR. Enhanced efficacy without further cleft closure: reevaluating twist as a source of agonist efficacy in AMPA receptors. J Neurosci. 2010 Jan 27;30(4):1463-70. PMID:20107073 doi:30/4/1463
Categories: Rattus norvegicus | Gill, A. | Madden, D R. | Ampa receptor | Cell junction | Cell membrane | Glua4 | Glycoprotein | Ion transport | Ionic channel | Kainate | L651v | Ligand-binding domain | Ligand-gated ion channel | Lipoprotein | Membrane | Palmitate | Postsynaptic cell membrane | Receptor | Synapse | Transmembrane | Transport | Transport protein
