8AYO: Open state GluA1/A2 AMPA receptor

Open state GluA1/A2 AMPA receptor in complex with TARP gamma 8 and ligand JNJ-61432059. 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: 14,512
Mol. weight: 493.52 kDa
Ligands: OIJ, POV, PLM, OLC
Released: 19 Apr 2023

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

Secondary structure: helices and β-sheets

8AYO contains 104 α-helices and 98 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.

Chain A: 21 helices, 20 β-strands

Element	Residues	Length	Sheet
β-strand	391-395	5	1
β-strand	403-404	2	2
α-helix	405	1
α-helix	413-416	4
β-strand	417-418	2	2
α-helix	420-432	13
β-strand	436-440	5	1
β-strand	447-449	3	3
β-strand	456-457	2	3
α-helix	458-464	7
β-strand	470-476	7	1
α-helix	479-482	4
β-strand	485-487	3	1
β-strand	493-495	3	4
β-strand	496-501	6	5
α-helix	502-504	3
α-helix	512-514	3
β-strand	517	1	6
α-helix	519-541	23
α-helix	569-581	13
α-helix	592-620	29
α-helix	632-637	6
β-strand	642-644	3	7
β-strand	646	1	8
α-helix	650-656	7
α-helix	661-671	11
β-strand	679	1	8
α-helix	682-690	9
β-strand	696-698	3	7
β-strand	699-701	3	5
α-helix	702-710	9
β-strand	716-719	4	5
β-strand	725-727	3	4
β-strand	728-733	6	1
α-helix	739-752	14
α-helix	754-760	7
α-helix	761-765	5
α-helix	782	1
β-strand	783	1	9
α-helix	784	1
α-helix	789-814	26

Chains B and D: 26 helices, 23 β-strands

Element	Residues	Length	Sheet
β-strand	394-399	6	31
β-strand	407-408	2	32
α-helix	409	1
α-helix	412-414	3
α-helix	417-420	4
β-strand	421-422	2	32
α-helix	424-436	13
β-strand	439-444	6	31
β-strand	451-453	3	33
β-strand	460-461	2	33
α-helix	462-469	8
β-strand	474	1	31
β-strand	475	1	34
α-helix	479	1
β-strand	480	1	35
α-helix	481	1
α-helix	483-488	6
β-strand	489-491	3	34
β-strand	496-499	4	35
β-strand	500-505	6	36
α-helix	506-509	4
β-strand	510	1	37
α-helix	511-513	3
α-helix	516-518	3
β-strand	521	1	9
α-helix	523-546	24
α-helix	573-584	12
α-helix	596-618	23
α-helix	620-625	6
β-strand	628	1	37
α-helix	636-641	6
β-strand	646-648	3	36
β-strand	650	1	38
α-helix	654-660	7
α-helix	665-676	12
β-strand	683	1	38
α-helix	686-694	9
β-strand	700-705	6	36
α-helix	706-713	8
β-strand	720-723	4	36
β-strand	729-732	4	35
β-strand	735-737	3	34
α-helix	743-756	14
α-helix	758-763	6
α-helix	764-768	5
α-helix	786	1
β-strand	787	1	24
α-helix	788	1
α-helix	793-818	26

Chain C: 21 helices, 20 β-strands

Element	Residues	Length	Sheet
β-strand	391-395	5	19
β-strand	403-404	2	20
α-helix	405	1
α-helix	413-416	4
β-strand	417-418	2	20
α-helix	420-432	13
β-strand	436-440	5	19
β-strand	447-449	3	21
β-strand	456-457	2	21
α-helix	458-464	7
β-strand	470-471	2	19
α-helix	479-484	6
β-strand	485-487	3	19
β-strand	493-495	3	22
β-strand	496-501	6	23
α-helix	502-504	3
α-helix	512-514	3
β-strand	517	1	24
α-helix	519-541	23
α-helix	569-581	13
α-helix	592-620	29
α-helix	632-637	6
β-strand	642-644	3	25
β-strand	646	1	26
α-helix	650-656	7
α-helix	661-671	11
β-strand	679	1	26
α-helix	682-690	9
β-strand	696-698	3	25
β-strand	699-701	3	23
α-helix	702-710	9
β-strand	716-719	4	23
β-strand	725-727	3	22
β-strand	731-733	3	19
α-helix	739-752	14
α-helix	754-760	7
α-helix	761-765	5
α-helix	782	1
β-strand	783	1	17
α-helix	784	1
α-helix	789-814	26

Chains I and J: 5 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	19-40	22
β-strand	45	1	27
β-strand	46-49	4	28
β-strand	80-83	4	28
β-strand	88-91	4	28
β-strand	100-102	3	28
α-helix	119-127	9
α-helix	129-150	22
α-helix	156-183	28
β-strand	201	1	27
α-helix	203-233	31

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
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)
Voltage-dependent calcium channel gamma-8 subunit	I, J	protein	423	Rattus norvegicus	Q8VHW5 (AlphaFold model)

Sequence of entity 1 (A, C), FASTA

>8AYO_1 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 2 (B, D), FASTA

>8AYO_2 Isoform Flip of Glutamate receptor 2 (chains B, D)
MQKIMHISVLLSPVLWGLIFGVSSNSIQIGGLFPRGADQEYSAFRVGMVQFSTSEFRLTP
HIDNLEVANSFAVTNAFCSQFSRGVYAIFGFYDKKSVNTITSFCGTLHVSFITPSFPTDG
THPFVIQMRPDLKGALLSLIEYYQWDKFAYLYDSDRGLSTLQAVLDSAAEKKWQVTAINV
GNINNDKKDETYRSLFQDLELKKERRVILDCERDKVNDIVDQVITIGKHVKGYHYIIANL
GFTDGDLLKIQFGGANVSGFQIVDYDDSLVSKFIERWSTLEEKEYPGAHTATIKYTSALT
YDAVQVMTEAFRNLRKQRIEISRRGNAGDCLANPAVPWGQGVEIERALKQVQVEGLSGNI
KFDQNGKRINYTINIMELKTNGPRKIGYWSEVDKMVVTLTELPSGNDTSGLENKTVVVTT
ILESPYVMMKKNHEMLEGNERYEGYCVDLAAEIAKHCGFKYKLTIVGDGKYGARDADTKI
WNGMVGELVYGKADIAIAPLTITLVREEVIDFSKPFMSLGISIMIKKPQKSKPGVFSFLD
PLAYEIWMCIVFAYIGVSVVLFLVSRFSPYEWHTEEFEDGRETQSSESTNEFGIFNSLWF
SLGAFMRQGCDISPRSLSGRIVGGVWWFFTLIIISSYTANLAAFLTVERMVSPIESAEDL
SKQTEIAYGTLDSGSTKEFFRRSKIAVFDKMWTYMRSAEPSVFVRTTAEGVARVRKSKGK
YAYLLESTMNEYIEQRKPCDTMKVGGNLDSKGYGIATPKGSSLGTPVNLAVLKLSEQGVL
DKLKNKWWYDKGECGAKDSGSKEKTSALSLSNVAGVFYILVGGLGLAMLVALIEFCYKSR
AEAKRMKVAKNPQNINPSSS

Sequence of entity 3 (I, J), FASTA

>8AYO_3 Voltage-dependent calcium channel gamma-8 subunit (chains I, J)
GESLKRWNEERGLWCEKGVQVLLTTIGAFAAFGLMTIAISTDYWLYTRALICNTTNLTAG
DDGPPHRGGSGSSEKKDPGGLTHSGLWRICCLEGLKRGVCVKINHFPEDTDYDHDSAEYL
LRVVRASSIFPILSAILLLLGGVCVAASRVYKSKRNIILGAGILFVAAGLSNIIGVIVYI
SANAGEPGPKRDEEKKNHYSYGWSFYFGGLSFILAEVIGVLAVNIYIERSREAHCQSRSD
LLKAGGGAGGSGGSGPSAILRLPSYRFRYRRRSRSSSRGSSEASPSRDASPGGPGGPGFA
STDISMYTLSRDPSKGSVAAGLASAGGGGGGAGVGAYGGAAGAAGGGGTGSERDRGSSAG
FLTLHNAFPKEAASGVTVTVTGPPAAPAPAPPAPAAPAPGTLSKEAAASNTNTLNRKLEV
LFQ

Ligands and cofactors

ID	Name	Formula	Copies
OIJ	5-[2-(4-fluorophenyl)-7-(4-oxidanylpiperidin-1-yl)pyrazolo[1,5-c]pyrimidin-3-yl…	C25 H22 F N5 O2	2
POV	(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl…	C42 H82 N O8 P	2
PLM	Palmitic acid	C16 H32 O2	10
OLC	(2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate	C21 H40 O4	4
CYZ	Cyclothiazide	C14 H16 Cl N3 O4 S2	4
GLU	Glutamic acid	C5 H9 N O4	4

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 P19490 (AlphaFold model), which also has an AlphaFold model), best resolution first:

2AWW 2.21 Å, Synapse associated protein 97 PDZ2 domain variant C378G with C-terminal GluR-A peptide
3SAJ 2.5 Å, Crystal Structure of glutamate receptor GluA1 Amino Terminal Domain
8C2H 2.64 Å, Transmembrane domain of active state homomeric GluA1 AMPA receptor in tandem with TARP…
8C2I 2.7 Å, Transmembrane domain of resting state homomeric GluA1 AMPA receptor in complex with TARP…
8AYN 2.8 Å, Resting state GluA1/A2 AMPA receptor in complex with TARP gamma 8 and ligand LY3130481
8C1Q 2.82 Å, Resting state homomeric GluA1 AMPA receptor in complex with TARP gamma 3
8C1P 2.9 Å, Active state homomeric GluA1 AMPA receptor in complex with TARP gamma 3
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
9OVU 3.2 Å, Composite map of GluA1/A2 in the activated state, in complex with positive allosteric…
9NR6 3.26 Å, The structure of Noelin 1 with cerebellar GluA1/A4-ATD
8AYM 3.3 Å, Resting state GluA1/A2 AMPA receptor in complex with TARP gamma 8 and ligand JNJ-55511118

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