title: Lessons from crystal structures of kainate receptors.
abstract: Kainate receptors belong to the family of ionotropic glutamate receptors. These receptors assemble from five subunits (GluK1-5) into tetrameric ion channels. Kainate receptors are located at both pre- and postsynaptic membranes in the central nervous system where they contribute to excitatory synaptic transmission and modulate network excitability by regulating neurotransmitter release. Dysfunction of kainate receptors has been implicated in several neurological disorders such as epilepsy, schizophrenia and depression. Here we provide a review on the current understanding of kainate receptor structure and how they bind agonists, antagonists and ions. The first structure of the ligand-binding domain of the GluK1 subunit was reported in 2005, seven years after publication of the crystal structure of a soluble construct of the ligand-binding domain of the AMPA-type subunit GluA2. Today, a full-length structure has been determined of GluK2 by cryo electron microscopy to 7.6 Å resolution as well as 84 high-resolution crystal structures of N-terminal domains and ligand-binding domains, including agonist and antagonist bound structures, modulatory ions and mutations. However, there are still many unanswered questions and challenges in front of us. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Jagtvej 162, DK-2100, Copenhagen Ø, Denmark.
authors.forename: Stine
authors.initials: S
authors.lastname: Møllerud
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Jagtvej 162, DK-2100, Copenhagen Ø, Denmark.
authors.forename: Karla
authors.initials: K
authors.lastname: Frydenvang
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Jagtvej 162, DK-2100, Copenhagen Ø, Denmark.
authors.forename: Darryl S
authors.initials: DS
authors.lastname: Pickering
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Jagtvej 162, DK-2100, Copenhagen Ø, Denmark. Electronic address: jsk@sund.ku.dk.
authors.forename: Jette Sandholm
authors.initials: JS
authors.lastname: Kastrup
mesh_terms: D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry; D018092:Kainic Acid Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D018683:Excitatory Amino Acid Agents; D008024:Ligands; D021122:Protein Subunits; D018092:Kainic Acid Receptors
keywords: (2S,4R)-4-methylglutamic acid (PubChem CID 95883); ATPO (PubChem CID 4615193); Crystal structures; Domoic acid (PubChem CID 5282253); Dysiherbaine (PubChem CID 9839436); Kainate receptors; Kainic acid (PubChem CID 10255); LY466195 (PubChem CID 10168249); Ligand-binding domain; Ligands; Mutations; N-terminal domain; Neodysiherbaine A (PubChem CID 11460505); Quisqualic acid (PubChem CID 1209); UBP310 (PubChem CID 6420160); l-glutamic acid (PubChem CID 33032)