8AYM: Resting state GluA1/A2 AMPA receptor

Resting state GluA1/A2 AMPA receptor in complex with TARP gamma 8 and ligand JNJ-55511118. Determined by electron microscopy at 3.3 Å resolution. Released 19 Apr 2023.

Method: Electron microscopy
Resolution: 3.3 Å
Organism: Rattus norvegicus
Chains: 6
Atoms: 15,962
Mol. weight: 496.13 kDa
Ligands: OLC, POV, ZK1, PLM
Released: 19 Apr 2023

Explore 8AYM in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8AYM contains 82 α-helices and 96 β-strands across 6 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chains A and C: 18 helices, 20 β-strands

Element	Residues	Length	Sheet
β-strand	391-392	2	28
β-strand	395	1	29
β-strand	403-404	2	30
α-helix	413-416	4
β-strand	417-418	2	30
α-helix	420-432	13
β-strand	436-437	2	28
β-strand	440	1	29
β-strand	447-450	4	31
β-strand	455-457	3	31
α-helix	458-464	7
β-strand	471-476	6	32
α-helix	479-484	6
β-strand	485-487	3	32
β-strand	492-494	3	32
β-strand	496-501	6	33
α-helix	502-503	2
β-strand	517	1	20
α-helix	519-540	22
α-helix	544-547	4
α-helix	569-580	12
α-helix	592-624	33
α-helix	632-637	6
β-strand	642-644	3	33
β-strand	646	1	34
α-helix	650-657	8
α-helix	661-672	12
β-strand	679	1	34
α-helix	682-691	10
β-strand	696-701	6	33
α-helix	702-709	8
β-strand	716-719	4	33
β-strand	726-733	8	32
α-helix	739-751	13
α-helix	754-760	7
α-helix	761-765	5
β-strand	783	1	26
α-helix	789-814	26

Chains B and D: 18 helices, 20 β-strands

Element	Residues	Length	Sheet
β-strand	396-398	3	21
β-strand	402	1	22
β-strand	406	1	22
β-strand	407-408	2	23
α-helix	417-420	4
β-strand	421-422	2	23
α-helix	424-436	13
β-strand	441-442	2	21
β-strand	453	1	24
β-strand	460	1	24
α-helix	462-468	7
β-strand	474-475	2	21
β-strand	480	1	21
α-helix	483-486	4
β-strand	489-498	10	21
β-strand	500-505	6	25
α-helix	510-513	4
β-strand	521	1	26
α-helix	523-546	24
α-helix	573-584	12
α-helix	596-625	30
α-helix	637-641	5
β-strand	646-648	3	25
β-strand	650	1	27
α-helix	654-661	8
α-helix	665-675	11
β-strand	683	1	27
α-helix	686-695	10
β-strand	700-705	6	25
α-helix	706-713	8
β-strand	720-723	4	25
β-strand	730-737	8	21
α-helix	743-756	14
α-helix	758-763	6
α-helix	764-768	5
α-helix	777-779	3
β-strand	787	1	11
α-helix	793-818	26

Chains I and J: 5 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	20-39	20
β-strand	45-46	2	1
β-strand	48	1	2
β-strand	81	1	2
β-strand	82	1	3
β-strand	88-90	3	4
β-strand	91	1	3
β-strand	100-102	3	4
α-helix	116-127	12
α-helix	129-149	21
α-helix	156-183	28
β-strand	200-201	2	1
α-helix	203-232	30

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Voltage-dependent calcium channel gamma-8 subunit	I, J	protein	423	Rattus norvegicus	Q8VHW5 (AlphaFold model)
Isoform Flip of Glutamate receptor 1	A, C	protein	915	Rattus norvegicus	P19490 (AlphaFold model)
Isoform Flip of Glutamate receptor 2	B, D	protein	860	Rattus norvegicus	P19491 (AlphaFold model)

Sequence of entity 1 (I, J), FASTA

>8AYM_1 Voltage-dependent calcium channel gamma-8 subunit (chains I, J)
GESLKRWNEERGLWCEKGVQVLLTTIGAFAAFGLMTIAISTDYWLYTRALICNTTNLTAG
DDGPPHRGGSGSSEKKDPGGLTHSGLWRICCLEGLKRGVCVKINHFPEDTDYDHDSAEYL
LRVVRASSIFPILSAILLLLGGVCVAASRVYKSKRNIILGAGILFVAAGLSNIIGVIVYI
SANAGEPGPKRDEEKKNHYSYGWSFYFGGLSFILAEVIGVLAVNIYIERSREAHCQSRSD
LLKAGGGAGGSGGSGPSAILRLPSYRFRYRRRSRSSSRGSSEASPSRDASPGGPGGPGFA
STDISMYTLSRDPSKGSVAAGLASAGGGGGGAGVGAYGGAAGAAGGGGTGSERDRGSSAG
FLTLHNAFPKEAASGVTVTVTGPPAAPAPAPPAPAAPAPGTLSKEAAASNTNTLNRKLEV
LFQ

Sequence of entity 2 (A, C), FASTA

>8AYM_2 Isoform Flip of Glutamate receptor 1 (chains A, C)
MPYIFAFFCTGFLGAVVGADYKDDDDKNFPNNIQIGGLFPNQQSQEHAAFRFALSQLTEP
PKLLPQIDIVNISDSFEMTYRFCSQFSKGVYAIFGFYERRTVNMLTSFCGALHVCFITPS
FPVDTSNQFVLQLRPELQEALISIIDHYKWQTFVYIYDADRGLSVLQRVLDTAAEKNWQV
TAVNILTTTEEGYRMLFQDLEKKKERLVVVDCESERLNAILGQIVKLEKNGIGYHYILAN
LGFMDIDLNKFKESGANVTGFQLVNYTDTIPARIMQQWRTSDSRDHTRVDWKRPKYTSAL
TYDGVKVMAEAFQSLRRQRIDISRRGNAGDCLANPAVPWGQGIDIQRALQQVRFEGLTGN
VQFNEKGRRTNYTLHVIEMKHDGIRKIGYWNEDDKFVPAATDAQAGGDNSSVQNRTYIVT
TILEDPYVMLKKNANQFEGNDRYEGYCVELAAEIAKHVGYSYRLEIVSDGKYGARDPDTK
AWNGMVGELVYGRADVAVAPLTITLVREEVIDFSKPFMSLGISIMIKKPQKSKPGVFSFL
DPLAYEIWMCIVFAYIGVSVVLFLVSRFSPYEWHSEEFEEGRDQTTSDQSNEFGIFNSLW
FSLGAFMQQGCDISPRSLSGRIVGGVWWFFTLIIISSYTANLAAFLTVERMVSPIESAED
LAKQTEIAYGTLEAGSTKEFFRRSKIAVFEKMWTYMKSAEPSVFVRTTEEGMIRVRKSKG
KYAYLLESTMNEYIEQRKPCDTMKVGGNLDSKGYGIATPKGSALRGPVNLAVLKLSEQGV
LDKLKSKWWYDKGECGSKDSGSKDKTSALSLSNVAGVFYILIGGLGLAMLVALIEFCYKS
RSESKRMKGFCLIPQQSINEAIRTSTLPRNSGAGASGGGGSGENGRVVSQDFPKSMQSIP
CMSHSSGMPLGATGL

Sequence of entity 3 (B, D), FASTA

>8AYM_3 Isoform Flip of Glutamate receptor 2 (chains B, D)
MQKIMHISVLLSPVLWGLIFGVSSNSIQIGGLFPRGADQEYSAFRVGMVQFSTSEFRLTP
HIDNLEVANSFAVTNAFCSQFSRGVYAIFGFYDKKSVNTITSFCGTLHVSFITPSFPTDG
THPFVIQMRPDLKGALLSLIEYYQWDKFAYLYDSDRGLSTLQAVLDSAAEKKWQVTAINV
GNINNDKKDETYRSLFQDLELKKERRVILDCERDKVNDIVDQVITIGKHVKGYHYIIANL
GFTDGDLLKIQFGGANVSGFQIVDYDDSLVSKFIERWSTLEEKEYPGAHTATIKYTSALT
YDAVQVMTEAFRNLRKQRIEISRRGNAGDCLANPAVPWGQGVEIERALKQVQVEGLSGNI
KFDQNGKRINYTINIMELKTNGPRKIGYWSEVDKMVVTLTELPSGNDTSGLENKTVVVTT
ILESPYVMMKKNHEMLEGNERYEGYCVDLAAEIAKHCGFKYKLTIVGDGKYGARDADTKI
WNGMVGELVYGKADIAIAPLTITLVREEVIDFSKPFMSLGISIMIKKPQKSKPGVFSFLD
PLAYEIWMCIVFAYIGVSVVLFLVSRFSPYEWHTEEFEDGRETQSSESTNEFGIFNSLWF
SLGAFMRQGCDISPRSLSGRIVGGVWWFFTLIIISSYTANLAAFLTVERMVSPIESAEDL
SKQTEIAYGTLDSGSTKEFFRRSKIAVFDKMWTYMRSAEPSVFVRTTAEGVARVRKSKGK
YAYLLESTMNEYIEQRKPCDTMKVGGNLDSKGYGIATPKGSSLGTPVNLAVLKLSEQGVL
DKLKNKWWYDKGECGAKDSGSKEKTSALSLSNVAGVFYILVGGLGLAMLVALIEFCYKSR
AEAKRMKVAKNPQNINPSSS

Ligands and cofactors

ID	Name	Formula	Copies
OLC	(2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate	C21 H40 O4	2
POV	(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl…	C42 H82 N O8 P	6
ZK1	{[7-morpholin-4-yl-2,3-dioxo-6-(trifluoromethyl)-3,4-dihydroquinoxalin-1(2H)-yl…	C14 H15 F3 N3 O6 P	4
PLM	Palmitic acid	C16 H32 O2	14
XVD	6-[2-chloro-6-(trifluoromethoxy)phenyl]-1H-benzimidazol-2-ol	C14 H8 Cl F3 N2 O2	2

Primary citation

Modulatory mechanisms of TARP gamma 8-selective AMPA receptor therapeutics. Zhang, D., Lape, R., Shaikh, S.A. et al. Nat Commun (2023) 14:1659-1659. DOI 10.1038/s41467-023-37259-5 · PubMed

Other PDB entries of the same protein (UniProt Q8VHW5 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8AYN 2.8 Å, Resting state GluA1/A2 AMPA receptor in complex with TARP gamma 8 and ligand LY3130481
7OCE 3.1 Å, Resting state GluA1/A2 AMPA receptor in complex with TARP gamma 8 and CNIH2 (LBD-TMD)
8AYL 3.2 Å, Resting state GluA1/A2 AMPA receptor in complex with TARP gamma 8 and ligand JNJ-61432059
8AYO 3.3 Å, Open state GluA1/A2 AMPA receptor in complex with TARP gamma 8 and ligand JNJ-61432059
7OCA 3.4 Å, Resting state full-length GluA1/A2 heterotertramer in complex with TARP gamma 8 and CNIH2
7OCD 3.5 Å, Resting state GluA1/A2 heterotetramer in complex with auxiliary subunit TARP gamma 8…
7QHB 3.5 Å, Active state of GluA1/2 in complex with TARP gamma 8, L-glutamate and CTZ
7OCF 3.6 Å, Active state GluA1/A2 AMPA receptor in complex with TARP gamma 8 and CNIH2 (LBD-TMD)
7QHH 3.6 Å, Desensitized state of GluA1/2 AMPA receptor in complex with TARP-gamma 8 (TMD-LBD)
6QKC 4.4 Å, GluA1/2 In complex with auxiliary subunit gamma-8
6QKZ 6.3 Å, Full length GluA1/2-gamma8 complex

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