7SRS: 5-HT2B receptor

5-HT2B receptor bound to LSD in complex with beta-arrestin1 obtained by cryo-electron microscopy (cryoEM). Determined by electron microscopy at 3.3 Å resolution. Released 21 Sept 2022.

Method: Electron microscopy
Resolution: 3.3 Å
Organisms: Mus musculus, Homo sapiens
Chains: 6
Atoms: 8,361
Mol. weight: 150.38 kDa
Ligands: 7LD, NAG
Released: 21 Sept 2022

Explore 7SRS in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7SRS contains 30 α-helices and 77 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 C: 9 helices, 28 β-strands

Element	Residues	Length	Sheet
β-strand	7-8	2	7
β-strand	9-12	4	8
β-strand	19-22	4	8
β-strand	26-28	3	9
β-strand	29	1	10
β-strand	34	1	10
β-strand	37-42	6	8
β-strand	52-63	12	11
α-helix	66-70	5
β-strand	75-87	13	11
α-helix	89-90	2
α-helix	99-107	9
β-strand	112-117	6	8
β-strand	127-129	3	11
β-strand	141-151	11	11
α-helix	157-158	2
α-helix	160-162	3
β-strand	163-168	6	11
β-strand	169-171	3	9
α-helix	180-182	3
β-strand	183-189	7	12
β-strand	196-203	8	12
β-strand	207-208	2	13
β-strand	214-222	9	12
β-strand	228-242	15	14
β-strand	246-258	13	14
β-strand	262	1	14
β-strand	266-274	9	12
β-strand	288-289	2	11
β-strand	300	1	11
α-helix	301-303	3
β-strand	317-329	13	14
β-strand	334-341	8	14
β-strand	342-343	2	13
α-helix	345-348	4
α-helix	351-353	3
β-strand	359	1	15

Chain H: 1 helix, 10 β-strands

Element	Residues	Length	Sheet
β-strand	6-10	5	16
β-strand	21-28	8	16
α-helix	32-34	3
β-strand	35-42	8	17
β-strand	48-55	8	17
β-strand	60-63	4	17
β-strand	71-76	6	16
β-strand	81-86	6	16
β-strand	95-103	9	17
β-strand	112-113	2	17
β-strand	117-119	3	17

Chain L: 2 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	5-8	4	18
β-strand	11-13	3	19
β-strand	20-26	7	18
β-strand	34-39	6	19
β-strand	46-50	5	19
β-strand	54-55	2	19
β-strand	63-68	6	18
β-strand	71-76	6	18
α-helix	81-83	3
β-strand	86-91	6	19
β-strand	94	1	15
α-helix	97	1
β-strand	98-99	2	19
β-strand	103-106	4	19

Chain P: 2 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	4-7	4	1
β-strand	10-12	3	2
β-strand	19-25	7	1
β-strand	32-37	6	2
β-strand	44-48	5	2
β-strand	52-53	2	2
α-helix	54	1
β-strand	61-66	6	1
β-strand	69-74	6	1
β-strand	84-89	6	2
α-helix	95	1
β-strand	96-97	2	2
β-strand	101-104	4	2

Chain Q: 1 helix, 14 β-strands

Element	Residues	Length	Sheet
β-strand	3-6	4	3
β-strand	10-12	3	4
β-strand	18-25	8	3
β-strand	34-39	6	5
β-strand	45-51	7	5
β-strand	58-60	3	5
α-helix	62-64	3
β-strand	68-73	6	3
β-strand	78-83	6	3
β-strand	93-98	6	5
β-strand	101-104	4	6
β-strand	109-112	4	6
β-strand	116-117	2	5
β-strand	121-122	2	5
β-strand	123-125	3	4

Chain R: 15 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	57-81	25
α-helix	90-102	13
α-helix	103-107	5
α-helix	108-116	9
α-helix	127-158	32
α-helix	160-166	7
α-helix	169-187	19
α-helix	189-192	4
β-strand	195-197	3	6
α-helix	202-204	3
α-helix	211-222	12
α-helix	223-227	5
α-helix	228-250	23
α-helix	316-349	34
α-helix	355-382	28
α-helix	385-396	12
β-strand	458-459	2	7

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Anti-5HT2BR Fab light chain	P	protein	209	Mus musculus
Anti-5HT2BR Fab heavy chain	Q	protein	218	Mus musculus
5-hydroxytryptamine receptor 2B	R	protein	333	Homo sapiens	P41595 (AlphaFold model)
Isoform 1B of Beta-arrestin-1	C	protein	367	Homo sapiens	P49407 (AlphaFold model)
Fab30 heavy chain	H	protein	119	Mus musculus
Fab30 light chain	L	protein	106	Mus musculus

Sequence of entity 1 (P), FASTA

>7SRS_1 Anti-5HT2BR Fab light chain (chains P)
DIVLIQSPAIMSASPGEKVTITCSASSSVSYMHWFQQKPGTSPKLWIYSTSNLASGVPAR
FSGSGSGTSYSLTISRMEAEDAATYYCQQRSSYPLTFGAGTKLEIKRTVAAPSVFIFPPS
DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL
SKADYEKHKVYACEVTHQGLPVTKSFNRG

Sequence of entity 2 (Q), FASTA

>7SRS_2 Anti-5HT2BR Fab heavy chain (chains Q)
EVQLQQSGPELVKPGASVKLSCKASGYTFTSSWMHWVKQRPGQGLEWIGNIYPSNGGTNY
NERFKSKATLTVDRSSNTAYMQLSSLTSEDSAVYFCARFGSFITTILTTYYNPVDYWGQG
TTLTVSSASTKGPSVFPLAPSTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS
GLYSLSSVVTVPASSLGTQTYICNVNHKPSNTKVDKKV

Sequence of entity 3 (R), FASTA

>7SRS_3 5-hydroxytryptamine receptor 2B (chains R)
TESIPEEMKQIVEEQGNKLHWAALLILMVIIPTIGGNTLVILAVSLEKKLQYATNYFLMS
LAVADLLVGLFVMPIALLTIMFEAMWPLPLVLCPAWLFLDVLFSTASIWHLCAISVDRYI
AIKKPIQANQYNSRATAFIKITVVWLISIGIAIPVPIKGIETDVDNPNNITCVLTKERFG
DFMLFGSLAAFFTPLAIMIVTYFLTIHALQKVRLLSGSRQTISNLQRASKVLGIVFFLFL
LMWCPFFITNITLVLCDSCNQTTLQMLLEIFVWIGYVSSGVNPLVYTLFNKTFRDAFGRY
ITCNYRATKSVKTPMRLRSSTIQSSSIILLDTL

Sequence of entity 4 (C), FASTA

>7SRS_4 Isoform 1B of Beta-arrestin-1 (chains C)
GDKGTRVFKKASPNGKLTVYLGKRDFVDHIDLVDPVDGVVLVDPEYLKERRVYVTLTCAF
RYGREDLDVLGLTFRKDLFVANVQSFPPAPEDKKPLTRLQERLIKKLGEHAYPFTFEIPP
NLPCSVTLQPGPEDTGKACGVDYEVKAFCAENLEEKIHKRNSVRLVIEKVQYAPERPGPQ
PTAETTRQFLMSDKPLHLEASLDKEIYYHGEPISVNVHVTNNTNKTVKKIKISVRQYADI
CLFNTAQYKCPVAMEEADDTVAPSSTFCKVYTLTPFLANNREKRGLALDGKLKHEDTNLA
SSTLLREGANREILGIIVSYKVKVKLVVSRGGDVAVELPFTLMHPKPKEEPPHREVPENE
TPVDTNL

Sequence of entity 5 (H), FASTA

>7SRS_5 Fab30 heavy chain (chains H)
VQLVESGGGLVQPGGSLRLSCAASGFNVYSSSIHWVRQAPGKGLRWVASISSYYGYTYYA
DSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSRQFWYSGLDYWGQGTLVTVSS

Sequence of entity 6 (L), FASTA

>7SRS_6 Fab30 light chain (chains L)
DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPS
RFSGSRSGTDFTLTISSLQPEDFATYYCQQYKYVPVTFGQGTKVEI

Ligands and cofactors

ID	Name	Formula	Copies
7LD	(8alpha)-N,N-diethyl-6-methyl-9,10-didehydroergoline-8-carboxamide	C20 H25 N3 O	1
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	1

Primary citation

Signaling snapshots of a serotonin receptor activated by the prototypical psychedelic LSD. Cao, C., Barros-Alvarez, X., Zhang, S. et al. Neuron (2022) 110:3154. DOI 10.1016/j.neuron.2022.08.006 · PubMed

Other PDB entries of the same protein (UniProt P41595 (AlphaFold model), which also has an AlphaFold model), best resolution first:

4IB4 2.7 Å, Crystal structure of the chimeric protein of 5-HT2B-BRIL in complex with ergotamine
7SRQ 2.7 Å, 5-HT2B receptor bound to LSD obtained by cryo-electron microscopy (cryoEM)
4NC3 2.8 Å, Crystal structure of the 5-HT2B receptor solved using serial femtosecond crystallography…
5TVN 2.9 Å, Crystal structure of the LSD-bound 5-HT2B receptor
7SRR 2.9 Å, 5-HT2B receptor bound to LSD in complex with heterotrimeric mini-Gq protein obtained by…
6DRY 2.92 Å, Structural Determinants of Activation and Biased Agonism at the 5-HT2B Receptor
9WNG 2.98 Å, 5HT2BR-fab heterotrimer in complex with a novel antagonist IHCH-2330
5TUD 3.0 Å, Structural Insights into the Extracellular Recognition of the Human Serotonin 2B…
6DRX 3.1 Å, Structural Determinants of Activation and Biased Agonism at the 5-HT2B Receptor
6DRZ 3.1 Å, Structural Determinants of Activation and Biased Agonism at the 5-HT2B Receptor
9WQB 3.18 Å, 5-HT2B receptor bound to IHCH-6122 in complex with an antibody obtained by cryo-electron…
6DS0 3.19 Å, Structural Determinants of Activation and Biased Agonism at the 5-HT2B Receptor

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