8UWL: 5-HT2AR

5-HT2AR bound to Lisuride in complex with a mini-Gq protein and an active-state stabilizing single-chain variable fragment (scFv16) obtained by cryo-electron microscopy (cryoEM). Determined by electron microscopy at 2.8 Å resolution. Released 29 May 2024.

Method: Electron microscopy
Resolution: 2.8 Å
Organism: Homo sapiens
Chains: 5
Atoms: 8,626
Mol. weight: 142.53 kDa
Ligands: H8G
Released: 29 May 2024

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

Secondary structure: helices and β-sheets

8UWL contains 35 α-helices and 59 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: 15 helices, 0 β-strands

Element	Residues	Length
α-helix	79-100	22
α-helix	108-125	18
α-helix	127-137	11
α-helix	145-147	3
α-helix	148-178	31
α-helix	180-185	6
α-helix	191-207	17
α-helix	210-214	5
α-helix	218-221	4
α-helix	234-239	6
α-helix	240-244	5
α-helix	245-265	21
α-helix	313-348	36
α-helix	356-382	27
α-helix	385-396	12

Chain B: 9 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	7-30	24
β-strand	34-39	6	1
α-helix	46-48	3
β-strand	70-76	7	1
β-strand	79-85	7	1
α-helix	96-98	3
β-strand	105-111	7	1
α-helix	118-129	12
β-strand	138-144	7	1
α-helix	146-155	10
α-helix	160-163	4
α-helix	165-167	3
α-helix	184-203	20
β-strand	211-215	5	1
α-helix	223-242	20

Chain C: 3 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	4-24	21
α-helix	30-33	4
α-helix	38-39	2
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	121-125	5	4
β-strand	134-139	6	4
β-strand	146-153	8	5
β-strand	156-161	6	5
β-strand	165-170	6	5
β-strand	175-181	7	5
β-strand	187-192	6	6
β-strand	198-203	6	6
β-strand	208-212	5	6
β-strand	217-222	6	6
β-strand	229-234	6	7
β-strand	240-245	6	7
β-strand	250-254	5	7
β-strand	259-264	6	7
β-strand	273-278	6	8
β-strand	284-289	6	8
β-strand	294-298	5	8
β-strand	304-308	5	8
β-strand	315-320	6	2
β-strand	327-331	5	2
β-strand	336-339	4	2

Chain D: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	10-23	14
α-helix	30-43	14
α-helix	45-47	3
α-helix	53-55	3

Chain E: 4 helices, 25 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	9
β-strand	11	1	10
β-strand	18-25	8	9
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	9
β-strand	78-83	6	9
α-helix	88-90	3
β-strand	92-99	8	11
β-strand	110-111	2	11
β-strand	115-117	3	11
β-strand	118	1	10
β-strand	128-129	2	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
β-strand	191-196	6	12
β-strand	199-204	6	12
β-strand	213-219	7	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 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

>8UWL_1 5-hydroxytryptamine receptor 2A (chains A)
LSLLHLQEKNWSALLTAVVIILTIAGNILVIMAVSLEKKLQNATNYFLMSLAIADMLLGF
LVMPVSMLTILYGYRWPLPSKLCAVWIYLDVLFSTASIMHLCAISLDRYVAIQNPIHHSR
FNSRTKAFLKIIAVWTISVGISMPIPVFGLQDDSKVFKEGSCLLADDNFVLIGSFVSFFI
PLTIMVITYFLTIKSLQKEATLCVSDLGTRAKLASFSFLPQSSLSSEKLFQRSIHREPGS
YTGRRTMQSISNEQKACKVLGIVFFLFVVMWCPFFITNIMAVICKESCNEDVIGALLNVF
VWIGYLSSAVNPLVYTLFNKTYRSAFSRYIQCQYKENKK

Sequence of entity 2 (B), FASTA

>8UWL_2 G protein subunit q (Gi2-mini-Gq chimera) (chains B)
MGSTVSAEDKAAAERSKMIDKNLREDGEKARRTLRLLLLGADNSGKSTIVKQMRILHGGS
GGSGGTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTAIIFVVDSSDYNRLQE
ALNDFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEP
GEDPRVTRAKYFIRKEFVDISTASGDGRHICYPHFTCAVDTENARRIFNDCKDIILQMNL
REYNLV

Sequence of entity 3 (C), FASTA

>8UWL_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

>8UWL_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains D)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 5 (E), FASTA

>8UWL_5 Single-chain variable fragment 16 (scFv16) (chains E)
MLLVNQSHQGFNKEHTSKMVSAIVLYVLLAAAAHSAFADVQLVESGGGLVQPGGSRKLSC
SASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYYADTVKGRFTISRDDPKNTLFLQ
MTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVSSGGGGSGGGGSGGGGSDIVMTQ
ATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQRPGQSPQLLIYRMSNLASGVPDR
FSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFGAGTKLELK

Ligands and cofactors

ID	Name	Formula	Copies
H8G	N,N-diethyl-N'-[(8alpha)-6-methyl-9,10-didehydroergolin-8-yl]urea	C20 H26 N4 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
9J87 2.84 Å, Structure of Receptor
9LL7 2.84 Å, DOI-bound Serotonin 2A (5-HT2A) receptor-Gi complex
6A94 2.9 Å, Crystal structure of 5-HT2AR in complex with zotepine

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