Table 2

Residues important for agonist recognition in rodent glutamate receptors

Subunit	Mutation	GluR2 Equivalent^2-a	Ligand Binding^2-b	Functional Effect of Mutation
NR1^2-a ^2-c	Q387K	E402	β	14,000× ↑ in glycine EC₅₀, 13× ↑ in glutamate EC₅₀
	F390S	Y405	δ	63× ↑ in glycine EC₅₀
	Y392A	M407		12× ↑ in glycine EC₅₀
	F466H	Y450	β^*	2,100× ↑ in glycine EC₅₀
	V666A	L650		13× ↑ in glycine EC₅₀
	S669G	G653	β	25× ↑ in glycine EC₅₀
NR1^2-d	F735A	L727		16× ↑ in glycine EC₅₀
	F736A	D728		28× ↑ in glycine EC₅₀
NR1^2-e	D481N	D447		7× ↑ in glycine EC₅₀
	K483Q	K449	β	130× ↑ in glycine EC₅₀
NR1^2-f	D732E	E705	α^*	3,700× ↑ in glycine EC₅₀
NR2B^2-g	E387A	E402	β	240× ↑ in glutamate EC₅₀
	F390S	Y405	δ	50× ↑ in glutamate EC₅₀
	K459E	K449	β	180× ↑ in glutamate EC₅₀
	H460F	Y450	β^*	9× ↑ in glutamate EC₅₀
	R493K	R485	α^*	Complete loss of agonist responses
	S486A	P478	β^*	43× ↑ in glutamate EC₅₀
	V660A	L650		20× ↑ in glutamate EC₅₀
	S664G	S654	α^*	100× ↑ in glutamate EC₅₀
	V709A	M708		30× ↑ in glutamate EC₅₀
NR2A^2-h	N463A	D447		6× ↑ in glutamate EC₅₀, no change in gly EC₅₀
	K465E	K449	β	10× ↑ in glutamate EC₅₀, no change in gly EC₅₀
	H466A	Y450	β^*	220× ↑ in glutamate EC₅₀, no change in gly EC₅₀
	T665A	T649		7× ↑ in glutamate EC₅₀, no change in gly EC₅₀
	V666A	L650		12× ↑ in glutamate EC₅₀, 1.7× ↑ in gly EC₅₀
	G669A	G653	β	320× ↑ in glutamate EC₅₀, no change in gly EC₅₀
	T671A	T655	α^*	1,000× ↑ in glutamate EC₅₀, no change in gly EC₅₀
GluR1^2-i	E398Q	E402	β	8× less sensitive to glutamate desensitization
	Y446F	Y450	β^*	4× less sensitive to glutamate desensitization
	L646A	L650		40× less sensitive to glutamate desensitization
	S650V	S654	α^*	18× less sensitive to glutamate desensitization
GluR1^2-j	E398K	E402	β	100,000× ↑ in glutamate EC₅₀
(mouse)	D443K	D447		5× ↑ in glutamate EC₅₀
	K445E	K449	β	22× ↑ in glutamate EC₅₀
GluR1^2-k	K445Q	K449	β	51× ↑ in AMPA EC₅₀, 3× ↑ in glutamate EC₅₀
GluR2^2-k	K449E	K449	β	4× ↑ in glutamate EC₅₀
GluR3^2-l	L507Y	L483		Abolishes glutamate desensitization
	T504A	T480	α^*	134× ↑ glutamate EC₅₀
GluR6^2-m	N721S	T686	β	2–3× ↑ glutamate affinity, >16× ↑ AMPA affinity
cKBP^2-n	E33V	E402	β	110× ↓ in kainate affinity, no change in glu affinity
	Y36F	Y405	δ	30× ↓ glutamate affinity, 5× ↓ kainate affinity
	Y73I	Y450	β^*	90× ↓ glutamate affinity, 10× ↓ kainate affinity
	P100A	P478	α^*	No significant change in kainate binding
	T102A	T480	α^*	100× ↓ glutamate affinity, 58× ↓ kainate affinity
	R107S	R485	α^*	Complete loss of kainate binding
	S266A	G653	β	5–6× ↓ kainate affinity
	S267A	S654	α^*	5–6× ↓ kainate affinity
	T268A	T655	α^*	Complete loss of kainate binding
	Y299A	T686	β	5–6× ↓ kainate affinity
	E316Q	E705	α^*	Complete loss of kainate binding

↵2-a The designated amino acid residues were mapped onto the rat GluR2 sequence numbered according to Armstrong et al. (1998).
↵2-b Residues identified in the crystal structure of the ligand-binding domain of GluR2. *, ligand-binding residues, α, residues interacting with all agonists; β, residues predicted to interact only with specific ligands; δ, residues that maintain the shape of the ligand-binding pocket but do not contact ligands. FromArmstrong et al. (1998).
↵2-c Kuryatov et al., 1994 (EC₅₀ measured in oocytes expressing NR1/NR2B receptors).
↵2-d Hirai et al., 1996 (EC₅₀ measured in oocytes expressing NR1/NR2B receptors).
↵2-e Wafford et al., 1995 (EC₅₀ measured from oocytes expressing NR1/NR2A receptors).
↵2-f Williams et al., 1996 (EC₅₀ measured in oocytes expressing NR1/NR2B receptors).
↵2-g Laube et al., 1997 (EC₅₀ measured in oocytes expressing NR1/NR2B receptors).
↵2-h Anson et al., 1998 (measured in oocytes expressing NR1/NR2A receptors).
↵2-i Mano et al., 1996 (EC₅₀ measured in oocytes expressing homomeric GluR1 receptors).
↵2-j Uchino et al., 1992 (EC₅₀ measured in oocytes expressing GluR1 receptors).
↵2-k Li et al., 1995 (EC₅₀ measured in oocytes expressing GluR1 or GluR1/GluR2 receptors).
↵2-l Stern-Bach et al., 1998 (EC₅₀ measured in outside-out patches of HEK293 cells expressing GluR3 receptors).
↵2-m Swanson et al., 1997b (EC₅₀ measured in oocytes expressing homomeric GluR6 receptors).
↵2-n Paas et al., 1996 (affinity judged by displacement of radiolabeled kainate from HEK 293 membranes).