Structure of a High-Affinity Kainate Receptor: GluK4 Ligand-Binding Domain Crystallized with Kainate

Ole Kristensen; Lise Baadsgaard Kristensen; Stine Møllerud; Karla Andrea Frydenvang; Darryl S Pickering; Jette Sandholm Jensen Kastrup

doi:10.1016/j.str.2016.06.019

Structure of a High-Affinity Kainate Receptor: GluK4 Ligand-Binding Domain Crystallized with Kainate

Ole Kristensen, Lise Baadsgaard Kristensen, Stine Møllerud, Karla Andrea Frydenvang, Darryl S Pickering, Jette Sandholm Jensen Kastrup

7 Citationer (Scopus)

Abstract

Ionotropic glutamate receptors play a key role in fast neurotransmission in the CNS and have been linked to several neurological diseases and disorders. One subfamily is the kainate receptors, which are grouped into low-affinity (GluK1-3) and high-affinity (GluK4-5) receptors based on their affinity for kainate. Although structures of the ligand-binding domain (LBD) of all low-affinity kainate receptors have been reported, no structures of the high-affinity receptor subunits are available. Here, we present the X-ray structure of GluK4-LBD with kainate at 2.05 Å resolution, together with thermofluor and radiolabel binding affinity data. Whereas binding-site residues in GluK4 are most similar to the AMPA receptor subfamily, the domain closure and D1-D2 interlobe contacts induced by kainate are similar to the low-affinity kainate receptor GluK1. These observations provide a likely explanation for the high binding affinity of kainate at GluK4-LBD.

Originalsprog	Engelsk
Tidsskrift	Structure
Vol/bind	24
Udgave nummer	9
Sider (fra-til)	1582-1589
Antal sider	8
ISSN	0969-2126
DOI	https://doi.org/10.1016/j.str.2016.06.019
Status	Udgivet - 6 sep. 2016

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10.1016/j.str.2016.06.019

http://www.cell.com/article/S0969212616301654/pdf

Citationsformater

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title = "Structure of a High-Affinity Kainate Receptor: GluK4 Ligand-Binding Domain Crystallized with Kainate",

abstract = "Ionotropic glutamate receptors play a key role in fast neurotransmission in the CNS and have been linked to several neurological diseases and disorders. One subfamily is the kainate receptors, which are grouped into low-affinity (GluK1-3) and high-affinity (GluK4-5) receptors based on their affinity for kainate. Although structures of the ligand-binding domain (LBD) of all low-affinity kainate receptors have been reported, no structures of the high-affinity receptor subunits are available. Here, we present the X-ray structure of GluK4-LBD with kainate at 2.05 {\AA} resolution, together with thermofluor and radiolabel binding affinity data. Whereas binding-site residues in GluK4 are most similar to the AMPA receptor subfamily, the domain closure and D1-D2 interlobe contacts induced by kainate are similar to the low-affinity kainate receptor GluK1. These observations provide a likely explanation for the high binding affinity of kainate at GluK4-LBD.",

author = "Ole Kristensen and Kristensen, {Lise Baadsgaard} and Stine M{\o}llerud and Frydenvang, {Karla Andrea} and Pickering, {Darryl S} and Kastrup, {Jette Sandholm Jensen}",

year = "2016",

month = sep,

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doi = "10.1016/j.str.2016.06.019",

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T1 - Structure of a High-Affinity Kainate Receptor: GluK4 Ligand-Binding Domain Crystallized with Kainate

AU - Kristensen, Ole

AU - Kristensen, Lise Baadsgaard

AU - Møllerud, Stine

AU - Frydenvang, Karla Andrea

AU - Pickering, Darryl S

AU - Kastrup, Jette Sandholm Jensen

PY - 2016/9/6

Y1 - 2016/9/6

N2 - Ionotropic glutamate receptors play a key role in fast neurotransmission in the CNS and have been linked to several neurological diseases and disorders. One subfamily is the kainate receptors, which are grouped into low-affinity (GluK1-3) and high-affinity (GluK4-5) receptors based on their affinity for kainate. Although structures of the ligand-binding domain (LBD) of all low-affinity kainate receptors have been reported, no structures of the high-affinity receptor subunits are available. Here, we present the X-ray structure of GluK4-LBD with kainate at 2.05 Å resolution, together with thermofluor and radiolabel binding affinity data. Whereas binding-site residues in GluK4 are most similar to the AMPA receptor subfamily, the domain closure and D1-D2 interlobe contacts induced by kainate are similar to the low-affinity kainate receptor GluK1. These observations provide a likely explanation for the high binding affinity of kainate at GluK4-LBD.

AB - Ionotropic glutamate receptors play a key role in fast neurotransmission in the CNS and have been linked to several neurological diseases and disorders. One subfamily is the kainate receptors, which are grouped into low-affinity (GluK1-3) and high-affinity (GluK4-5) receptors based on their affinity for kainate. Although structures of the ligand-binding domain (LBD) of all low-affinity kainate receptors have been reported, no structures of the high-affinity receptor subunits are available. Here, we present the X-ray structure of GluK4-LBD with kainate at 2.05 Å resolution, together with thermofluor and radiolabel binding affinity data. Whereas binding-site residues in GluK4 are most similar to the AMPA receptor subfamily, the domain closure and D1-D2 interlobe contacts induced by kainate are similar to the low-affinity kainate receptor GluK1. These observations provide a likely explanation for the high binding affinity of kainate at GluK4-LBD.

U2 - 10.1016/j.str.2016.06.019

DO - 10.1016/j.str.2016.06.019

M3 - Journal article

C2 - 27524200

SN - 0969-2126

VL - 24

SP - 1582

EP - 1589

JO - Structure

JF - Structure

IS - 9

ER -

Structure of a High-Affinity Kainate Receptor: GluK4 Ligand-Binding Domain Crystallized with Kainate

Abstract

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