Lessons from crystal structures of kainate receptors

- Kainate receptors belong to the family of ionotropic glutamate receptors.
- These receptors are important for memory and learning.
- A review on 84 crystal structures of kainate receptors is presented.
- We discuss binding of agonists, antagonists, ions and mutations.

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'.

Kainate receptors contribute to fast excitatory neurotransmission and have been linked to brain diseases. We provide a review on 84 crystal structures of N-terminal and ligand-binding domains of kainate receptors.