8YN8: Histamine H3 receptor

Cryo-EM structure of histamine H3 receptor in complex with proxyfan and miniGo. Determined by electron microscopy at 2.77 Å resolution. Released 16 Oct 2024.

Method: Electron microscopy
Resolution: 2.77 Å
Organisms: synthetic construct, Homo sapiens
Chains: 5
Atoms: 8,864
Mol. weight: 176.09 kDa
Ligands: A1LY3, CLR
Released: 16 Oct 2024

Explore 8YN8 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8YN8 contains 37 α-helices and 61 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: 10 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	7-31	25
β-strand	33-40	8	1
α-helix	46-48	3
β-strand	54-55	2	1
α-helix	185	1
β-strand	186-191	6	1
β-strand	196-201	6	1
α-helix	209-211	3
α-helix	213-216	4
β-strand	221-227	7	1
α-helix	244-255	12
β-strand	264-270	7	1
α-helix	272-278	7
α-helix	284-286	3
α-helix	297-309	13
β-strand	319	1	1
β-strand	322-323	2	1
α-helix	331-350	20

Chain B: 3 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	3-24	22
α-helix	30-33	4
α-helix	38-39	2
β-strand	46-51	6	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	146-151	6	5
β-strand	156-161	6	5
β-strand	166-170	5	5
β-strand	175-180	6	5
β-strand	187-192	6	6
β-strand	198-203	6	6
β-strand	207-212	6	6
β-strand	218-223	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	336-340	5	2

Chain C: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	7-23	17
α-helix	30-43	14
α-helix	53-55	3
α-helix	56-58	3

Chain E: 5 helices, 25 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	9
β-strand	11-12	2	10
β-strand	18-25	8	9
α-helix	29-31	3
β-strand	33-39	7	11
β-strand	45-51	7	11
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	118-119	2	10
α-helix	138-139	2
β-strand	140-141	2	12
β-strand	146-148	3	13
β-strand	155-161	7	12
β-strand	166	1	14
β-strand	172	1	14
β-strand	174-179	6	13
β-strand	186-190	5	13
β-strand	194-195	2	13
α-helix	196	1
β-strand	203-208	6	12
β-strand	211-216	6	12
β-strand	226-231	6	13
α-helix	237	1
β-strand	239	1	13
β-strand	243-246	4	13

Chain R: 15 helices, 0 β-strands

Element	Residues	Length
α-helix	35-61	27
α-helix	68-82	15
α-helix	83-87	5
α-helix	88-96	9
α-helix	104-137	34
α-helix	139-145	7
α-helix	149-178	30
α-helix	183-184	2
α-helix	191-193	3
α-helix	197-203	7
α-helix	204-208	5
α-helix	209-233	25
α-helix	344-384	41
α-helix	391-415	25
α-helix	417-426	10

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Engineered guanine nucleotide-binding protein G(o) subunit alpha,Guanine nucleotide-binding…	A	protein	226	synthetic construct, Homo sapiens	P09471 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	376	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	C	protein	71	Homo sapiens	P59768 (AlphaFold model)
Antibody fragment scFv16	E	protein	255	synthetic construct
Histamine H3 receptor	R	protein	659	Homo sapiens	Q9Y5N1 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8YN8_1 Engineered guanine nucleotide-binding protein G(o) subunit alpha,Guanine nucleotide-binding protein G(o) subunit alpha (chains A)
MTLSAEERAALERSKAIEKNLKEDGISAAKDVKLLLLGADNSGKSTIVKQMKIIHGGSGG
SGGTTGIVETHFTFKNLHFRLFDVGGQRSERKKWIHCFEDVTAIIFCVDLSDYNRMHESL
MLFDSICNNKFFIDTSIILFLNKKDLFGEKIKKSPLTICFPEYTGPNTYEDAAAYIQAQF
ESKNRSPNKEIYCHMTCATDTNNAQVIFDAVTDIIIANNLRGCGLY

Sequence of entity 2 (B), FASTA

>8YN8_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MHHHHHHGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRT
LRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGN
YVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWD
IETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDIN
AICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYD
DFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWNGSSGGGGSGG
GGSSGVSGWRLFKKIS

Sequence of entity 3 (C), FASTA

>8YN8_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains C)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (E), FASTA

>8YN8_4 Antibody fragment scFv16 (chains E)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELLEENLYFQ

Sequence of entity 5 (R), FASTA

>8YN8_5 Histamine H3 receptor (chains R)
DYKDDDDHHHHHHHHGQPGNGSAFLLAPNGSHAPDHNVTQQRDEENLYFQGVDMERAPPD
GPLNASGALAGEAAAAGGARGFSAAWTAVLAALMALLIVATVLGNALVMLAFVADSSLRT
QNNFFLLNLAISDFLVGAFCIPLYVPYVLTGRWTFGRGLCKLWLVVDYLLCTSSAFNIVL
ISYDRFLSVTRAVSYRAQQGDTRRAVRKMLLVWVLAFLLYGPAILSWEYLSGGSSIPEGH
CYAEFFYNWYFLITASTLEFFTPFLSVTFFNLSIYLNIQRRTRLRLDGAREAAGPEPPPE
AQPSPPPPPGCWGCWQKGHGEAMPLHRYGVGEAAVGAEAGEATLGGGGGGGSVASPTSSS
GSSSRGTERPRSLKRGSKPSASSASLEKRMKMVSQSFTQRFRLSRDRKVAKSLAVIVSIF
GLCWAPYTLLMIIRAACHGHCVPDYWYETSFWLLWANSAVNPVLYPLCHHSFRRAFTKLL
CPQKLKIQPHSSLEHCWKAAAVFTLEDFVGDWEQTAAYNLDQVLEQGGVSSLLQNLAVSV
TPIQRIVRSGENALKIDIHVIIPYEGLSADQMAQIEEVFKVVYPVDDHHFKVILPYGTLV
IDGVTPNMLNYFGRPYEGIAVFDGKKITVTGTLWNGNKIIDERLITPDGSMLFRVTINS

Ligands and cofactors

ID	Name	Formula	Copies
A1LY3	5-(3-phenylmethoxypropyl)-1H-imidazole	C13 H16 N2 O	1
CLR	Cholesterol	C27 H46 O	5

Primary citation

Structural basis of ligand recognition and activation of the histamine receptor family. Zhang, X., Liu, G., Zhong, Y.N. et al. Nat Commun (2024) 15:8296-8296. DOI 10.1038/s41467-024-52585-y · PubMed

Other PDB entries of the same protein (UniProt P09471 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9BSB 2.32 Å, Global reconstruction of DRD2 bound to LSD in complex with a mini-GoA and scFv16…
9VJE 2.47 Å, Cryo-EM structure of 5-HT1AR-GoA in complex with buspirone
9K20 2.65 Å, Cryo-EM structure of ATP-bound P2Y purinoceptor 2-miniGo-scFv16 complex
9VJ5 2.69 Å, Cryo-EM structure of 5-HT1AR-GoA in complex with gepirone
8E9X 2.7 Å, CryoEM structure of miniGo-coupled hM4Di in complex with DCZ
9T88 2.74 Å, Cryo-EM structure of ESG-2-37-bound D3 dopamine receptor with mini-Go
9VNF 2.74 Å, Cryo-EM structure of 5-HT1AR-GoA in complex with (S)-pindolol
8YN7 2.77 Å, Cryo-EM structure of histamine H3 receptor in complex with immethridine and miniGo
9KVP 2.79 Å, Structure of SB290157 bound to human C3aR in complex with Go (Full map)
7W2Z 2.8 Å, Cryo-EM structure of the ghrelin-bound human ghrelin receptor-Go complex
8XXH 2.8 Å, Structure of CXCR2 bound to CXCL2 (CXCR2-CXCL2-Go Full map)
9PLO 2.8 Å, Structure of alpha2a adrenergic receptor in complex with Go heterotrimer, scFv16, and…

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