9L8L: GPCR megacomplex

Structure of GPCR megacomplex bound to agonists. Determined by electron microscopy at 3.22 Å resolution. Released 31 Dec 2025.

Method: Electron microscopy
Resolution: 3.22 Å
Organisms: Bos taurus, Rattus norvegicus, Homo sapiens
Chains: 5
Atoms: 8,997
Mol. weight: 184.88 kDa
Ligands: P0G, DR7
Released: 31 Dec 2025

Explore 9L8L in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9L8L contains 32 α-helices and 71 β-strands across 5 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: 7 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	12-38	27
β-strand	40-46	7	1
β-strand	209	1	1
β-strand	212-214	3	1
β-strand	217-223	7	1
α-helix	232-235	4
β-strand	244-249	6	1
α-helix	265-278	14
α-helix	280-282	3
β-strand	287-292	6	1
α-helix	294-303	10
α-helix	332-351	20
β-strand	359-360	2	1
β-strand	363	1	1
α-helix	371-390	20

Chain B: 3 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	2-24	23
α-helix	38-41	4
β-strand	47-51	5	2
β-strand	58-63	6	3
β-strand	69-74	6	3
β-strand	78-83	6	3
β-strand	88-94	7	3
β-strand	100-105	6	4
β-strand	111-116	6	4
β-strand	123-125	3	4
α-helix	133	1
β-strand	134-135	2	4
β-strand	146-151	6	5
β-strand	157-161	5	5
β-strand	166-168	3	5
β-strand	178-180	3	5
β-strand	187-191	5	6
β-strand	198-203	6	6
β-strand	207-212	6	6
β-strand	221-223	3	6
β-strand	229-234	6	7
β-strand	240-245	6	7
β-strand	252-254	3	7
β-strand	259-262	4	7
β-strand	276-277	2	8
β-strand	284-288	5	8
β-strand	294-298	5	8
β-strand	304-307	4	8
β-strand	317-320	4	2
β-strand	327-330	4	2
β-strand	336-339	4	2

Chain C: 4 helices, 35 β-strands

Element	Residues	Length	Sheet
β-strand	9-10	2	9
β-strand	19-22	4	9
β-strand	26-28	3	10
β-strand	37-42	6	9
β-strand	53-58	6	11
β-strand	61	1	12
β-strand	77	1	12
β-strand	81-85	5	11
α-helix	99-108	10
β-strand	112-117	6	9
β-strand	127-129	3	13
α-helix	130-131	2
β-strand	132	1	14
β-strand	135	1	14
β-strand	141	1	13
β-strand	142	1	12
β-strand	144	1	15
β-strand	148-150	3	11
β-strand	163-164	2	11
β-strand	168	1	15
β-strand	169-171	3	10
β-strand	183	1	16
β-strand	186	1	17
β-strand	199	1	17
β-strand	202-203	2	16
β-strand	207-208	2	18
β-strand	214-217	4	16
β-strand	220	1	19
β-strand	232-241	10	20
β-strand	251-256	6	20
β-strand	268	1	19
β-strand	271-274	4	16
β-strand	288-290	3	13
β-strand	300	1	13
α-helix	301-305	5
α-helix	307-309	3
β-strand	317-327	11	20
β-strand	343-349	7	20
β-strand	350-351	2	18

Chain G: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	11-21	11
α-helix	22-24	3
α-helix	30-43	14

Chain R: 15 helices, 0 β-strands

Element	Residues	Length
α-helix	31-60	30
α-helix	62-64	3
α-helix	67-85	19
α-helix	87-95	9
α-helix	103-136	34
α-helix	138-144	7
α-helix	147-171	25
α-helix	182-186	5
α-helix	197-204	8
α-helix	205-209	5
α-helix	210-237	28
α-helix	272-298	27
α-helix	305-316	12
α-helix	318-326	9
α-helix	330-338	9

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short	A	protein	394	Bos taurus	P04896 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	351	Rattus norvegicus	P54311 (AlphaFold model)
Beta-arrestin-1	C	protein	392	Homo sapiens	P49407 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	68	Bos taurus	P63212 (AlphaFold model)
Beta-2 adrenergic receptor	R	protein	421	Homo sapiens	P07550

Sequence of entity 1 (A), FASTA

>9L8L_1 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains A)
MGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGAGESGKSTIVKQM
RILHVNGFNGEGGEEDPQAARSNSDGEKATKVQDIKNNLKEAIETIVAAMSNLVPPVELA
NPENQFRVDYILSVMNVPDFDFPPEFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLD
KIDVIKQDDYVPSDQDLLRCRVLTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFND
VTAIIFVVASSSYNMVIREDNQTNRLQEALNLFKSIWNNRWLRTISVILFLNKQDLLAEK
VLAGKSKIEDYFPEFARYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCY
PHFTCAVDTENIRRVFNDCRDIIQRMHLRQYELL

Sequence of entity 2 (B), FASTA

>9L8L_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MHHHHHHGSLLQSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRR
TLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSG
NYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALW
DIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDI
NAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGY
DDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (C), FASTA

>9L8L_3 Beta-arrestin-1 (chains C)
GDKGTRVFKKASPNGKLTVYLGKRDFVDHIDLVDPVDGVVLVDPEYLKERRVYVTLTCAF
RYGREDLDVLGLTFRKDLFVANVQSFPPAPEDKKPLTRLQERLIKKLGEHAYPFTFEIPP
NLPCSVTLQPGPEDTGKACGVDYEVKAFCAENLEEKIHKRNSVRLVIRKVQYAPERPGPQ
PTAETTRQFLMSDKPLHLEASLDKEIYYHGEPISVNVHVTNNTNKTVKKIKISVRQYADI
CLFNTAQYKCPVAMEEADDTVAPSSTFCKVYTLTPFLANNREKRGLALDGKLKHEDTNLA
SSTLLREGANREILGIIVSYKVKVKLVVSRGGLLGDLASSDVAVELPFTLMHPKPKEEPP
HREVPENETPVDTNLIELDTNDDDIVFEDFAR

Sequence of entity 4 (G), FASTA

>9L8L_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFC

Sequence of entity 5 (R), FASTA

>9L8L_5 Beta-2 adrenergic receptor (chains R)
DYKDDDDAMGQPGNGSAFLLAPNRSHAPDHDVTQQRDEVWVVGMGIVMSLIVLAIVFGNV
LVITAIAKFERLQTVTNYFITSLACADLVMGLAVVPFGAAHILMKMWTFGNFWCEFWTSI
DVLCVTASIETLCVIAVDRYFAITSPFKYQSLLTKNKARVIILMVWIVSGLTSFLPIQMH
WYRATHQEAINCYANETCCDFFTNQAYAIASSIVSFYVPLVIMVFVYSRVFQEAKRQLQK
IDKSEGRFHVQNLSQVEQDGRTGHGLRRSSKFCLKEHKALRTLSVIMGTFTLCWLPFFIV
NIVHVIQDNLIRKEVYILLNWIGYVNSGFNPLIYCRSPDFRIAFQELLCLRRSSLKAYGN
GYSSNGNTGEQSGYHVEQEKENKLLCEDLPGTEDFVGHQGTVPSDNIDSQGRNCSTNDSL
L

Ligands and cofactors

ID	Name	Formula	Copies
P0G	8-[(1R)-2-{[1,1-dimethyl-2-(2-methylphenyl)ethyl]amino}-1-hydroxyethyl]-5-hydro…	C21 H26 N2 O4	1
DR7	(3S,8S,9S,12S)-3,12-BIS(1,1-dimethylethyl)-8-hydroxy-4,11-dioxo-9-(phenylmethyl…	C38 H52 N6 O7	1

Primary citation

A GPCR-G protein-beta-arrestin megacomplex enabled by a versatile allosteric modulator. He, G., Sun, Q., Xu, X. et al. Cell (2026) 189:1434-1450.e22. DOI 10.1016/j.cell.2025.12.023 · PubMed

Other PDB entries of the same protein (UniProt P04896 (AlphaFold model), which also has an AlphaFold model), best resolution first:

1AZS 2.3 Å, Complex of gs-alpha with the catalytic domains of mammalian adenylyl cyclase
1AZT 2.3 Å, Gs-alpha complexed with GTP-gamma-S
9IJE 2.34 Å, Epinephrine-activated human beta3 adrenergic receptor
1CUL 2.4 Å, Complex of gs-alpha with the catalytic domains of mammalian adenylyl cyclase: complex…
1CS4 2.5 Å, Complex of gs-alpha with the catalytic domains of mammalian adenylyl cyclase: complex…
8DCS 2.5 Å, Cryo-EM structure of cyanopindolol-bound beta1-adrenergic receptor in complex with…
7JJO 2.6 Å, Structural Basis of the Activation of Heterotrimeric Gs-protein by Isoproterenol-bound…
8DCR 2.6 Å, Cryo-EM structure of dobutamine-bound beta1-adrenergic receptor in complex with…
7X8R 2.61 Å, Cryo-EM structure of the Boc5-bound hGLP-1R-Gs complex
3C14 2.68 Å, Complex of GS-Alpha with the Catalytic Domains of Mammalian Adenylyl Cyclase: Complex…
7VQX 2.74 Å, Cryo-EM structure of human vasoactive intestinal polypeptide receptor 2 (VIP2R) in…
8X9T 2.75 Å, Identification, structure and agonist design of an androgen membrane receptor

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