8V6U: 5HT2AR-miniGq heterotrimer

5HT2AR-miniGq heterotrimer in complex with a novel agonist obtained from large scale docking. Determined by electron microscopy at 3.0 Å resolution. Released 29 May 2024.

Method: Electron microscopy
Resolution: 3.0 Å
Organism: Homo sapiens
Chains: 5
Atoms: 8,211
Mol. weight: 142.47 kDa
Ligands: YEQ
Released: 29 May 2024

Explore 8V6U in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8V6U contains 39 α-helices and 60 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: 17 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	79-101	23
α-helix	110-126	17
α-helix	128-136	9
α-helix	145-147	3
α-helix	148-178	31
α-helix	180-185	6
α-helix	190-206	17
α-helix	209-214	6
β-strand	222	1	1
β-strand	227	1	1
α-helix	232-239	8
α-helix	240-244	5
α-helix	245-261	17
α-helix	318-334	17
α-helix	337-348	12
α-helix	356-371	16
α-helix	372-374	3
α-helix	376-379	4
α-helix	385-392	8

Chain B: 9 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	7-31	25
β-strand	34-39	6	2
α-helix	46-48	3
β-strand	69-76	8	2
β-strand	79-86	8	2
α-helix	96-100	5
β-strand	105-111	7	2
α-helix	118-130	13
β-strand	138-144	7	2
α-helix	146-155	10
α-helix	160-162	3
α-helix	165-168	4
α-helix	184-202	19
β-strand	211-215	5	2
α-helix	223-242	20

Chain C: 4 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	6-24	19
α-helix	30-33	4
α-helix	38-39	2
β-strand	47-51	5	3
β-strand	58-63	6	4
β-strand	69-74	6	4
β-strand	78-83	6	4
β-strand	89-94	6	4
β-strand	100-105	6	5
β-strand	111-116	6	5
β-strand	120-125	6	5
β-strand	134-140	7	5
β-strand	146-151	6	6
β-strand	156-161	6	6
β-strand	166-170	5	6
β-strand	175-180	6	6
β-strand	187-192	6	7
β-strand	198-203	6	7
β-strand	207-212	6	7
β-strand	217-222	6	7
β-strand	229-234	6	8
β-strand	240-245	6	8
β-strand	250-254	5	8
β-strand	259-264	6	8
α-helix	272	1
β-strand	273-278	6	9
β-strand	284-289	6	9
β-strand	293-298	6	9
β-strand	304-309	6	9
β-strand	315-320	6	3
β-strand	327-331	5	3
β-strand	336-339	4	3

Chain D: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	12-22	11
α-helix	30-43	14
α-helix	53-55	3

Chain E: 6 helices, 24 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	10
β-strand	10-12	3	11
β-strand	17-25	9	10
α-helix	29-31	3
β-strand	33-39	7	11
β-strand	45-51	7	11
α-helix	53-55	3
β-strand	58-60	3	11
β-strand	68-73	6	10
α-helix	74-76	3
β-strand	78-84	7	10
α-helix	88-90	3
β-strand	92-99	8	11
β-strand	110-111	2	11
β-strand	115-119	5	11
β-strand	128-130	3	12
β-strand	134-136	3	13
β-strand	143-149	7	12
β-strand	154	1	14
β-strand	160	1	14
β-strand	162-167	6	13
β-strand	174-178	5	13
β-strand	182-183	2	13
α-helix	184	1
β-strand	191-195	5	12
β-strand	199-204	6	12
β-strand	214-219	6	13
α-helix	225	1
β-strand	226-227	2	13
β-strand	231-234	4	13

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
5-hydroxytryptamine receptor 2A	A	protein	339	Homo sapiens	P28223 (AlphaFold model)
G protein alpha-subunit q (Gi2-mini-Gq chimera)	B	protein	246	Homo sapiens
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	C	protein	340	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	D	protein	71	Homo sapiens	P59768 (AlphaFold model)
single-chain variable fragment 16 (scFv16)	E	protein	286	Homo sapiens

Sequence of entity 1 (A), FASTA

>8V6U_1 5-hydroxytryptamine receptor 2A (chains A)
LSLLHLQEKNWSALLTAVVIILTIAGNILVIMAVSLEKKLQNATNYFLMSLAIADMLLGF
LVMPVSMLTILYGYRWPLPSKLCAVWIYLDVLFSTASIMHLCAISLDRYVAIQNPIHHSR
FNSRTKAFLKIIAVWTISVGISMPIPVFGLQDDSKVFKEGSCLLADDNFVLIGSFVSFFI
PLTIMVITYFLTIKSLQKEATLCVSDLGTRAKLASFSFLPQSSLSSEKLFQRSIHREPGS
YTGRRTMQSISNEQKACKVLGIVFFLFVVMWCPFFITNIMAVICKESCNEDVIGALLNVF
VWIGYLSSAVNPLVYTLFNKTYRSAFSRYIQCQYKENKK

Sequence of entity 2 (B), FASTA

>8V6U_2 G protein alpha-subunit q (Gi2-mini-Gq chimera) (chains B)
MGSTVSAEDKAAAERSKMIDKNLREDGEKARRTLRLLLLGADNSGKSTIVKQMRILHGGS
GGSGGTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTAIIFVVDSSDYNRLQE
ALNDFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEP
GEDPRVTRAKYFIRKEFVDISTASGDGRHICYPHFTCAVDTENARRIFNDCKDIILQMNL
REYNLV

Sequence of entity 3 (C), FASTA

>8V6U_3 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains C)
MSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHLAKIYA
MHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACGGLDNI
CSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQQTTTF
TGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFFPNGNA
FATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCNVWDAL
KADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 4 (D), FASTA

>8V6U_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains D)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 5 (E), FASTA

>8V6U_5 single-chain variable fragment 16 (scFv16) (chains E)
MLLVNQSHQGFNKEHTSKMVSAIVLYVLLAAAAHSAFADVQLVESGGGLVQPGGSRKLSC
SASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYYADTVKGRFTISRDDPKNTLFLQ
MTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVSSGGGGSGGGGSGGGGSDIVMTQ
ATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQRPGQSPQLLIYRMSNLASGVPDR
FSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFGAGTKLELK

Ligands and cofactors

ID	Name	Formula	Copies
YEQ	4-{(3R)-1-[(1R)-1-(pyrimidin-2-yl)ethyl]piperidin-3-yl}phenol	C17 H21 N3 O	1

Primary citation

AlphaFold2 structures guide prospective ligand discovery. Lyu, J., Kapolka, N., Gumpper, R. et al. Science (2024) 384:eadn6354-eadn6354. DOI 10.1126/science.adn6354 · PubMed

Other PDB entries of the same protein (UniProt P28223 (AlphaFold model), which also has an AlphaFold model), best resolution first:

7WC8 2.45 Å, Crystal structure of serotonin 2A receptor in complex with lumateperone
7WC9 2.5 Å, Crystal structure of serotonin 2A receptor in complex with non-hallucinogenic…
9AS8 2.54 Å, Global reconstruction of 5-HT2AR bound to psilocin in complex with a mini-Gq protein and…
7WC6 2.6 Å, Crystal structure of serotonin 2A receptor in complex with LSD
7WC7 2.6 Å, Crystal structure of serotonin 2A receptor in complex with lisuride
9LL8 2.62 Å, Psilocin-bound Serotonin 2A (5-HT2A) receptor-Gi complex
8JT8 2.7 Å, Crystal structure of 5-HT2AR in complex with (R)-IHCH-7179
9AS7 2.72 Å, Local refinement of 5-HT2AR bound to psilocin in complex with a mini-Gq and scFv16…
9LL9 2.76 Å, DOI-bound Serotonin 2A (5-HT2A) receptor-Gq complex
8UWL 2.8 Å, 5-HT2AR bound to Lisuride in complex with a mini-Gq protein and an active-state…
9J87 2.84 Å, Structure of Receptor
9LL7 2.84 Å, DOI-bound Serotonin 2A (5-HT2A) receptor-Gi complex

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