8YN6: Histamine H3 receptor

Cryo-EM structure of histamine H3 receptor in complex with imetit and Gi. Determined by electron microscopy at 2.77 Å resolution. Released 9 Oct 2024.

Method: Electron microscopy
Resolution: 2.77 Å
Organisms: Homo sapiens, synthetic construct
Chains: 5
Atoms: 8,942
Mol. weight: 191.17 kDa
Ligands: ITF, CLR
Released: 9 Oct 2024

Explore 8YN6 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8YN6 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: 11 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	7-31	25
β-strand	33-40	8	1
α-helix	46-53	8
β-strand	185-190	6	1
β-strand	195-200	6	1
α-helix	208-210	3
α-helix	212-215	4
β-strand	220-226	7	1
α-helix	227-230	4
β-strand	233	1	2
β-strand	241	1	2
α-helix	242-254	13
α-helix	257-259	3
β-strand	263-269	7	1
α-helix	271-280	10
α-helix	283-285	3
α-helix	296-309	14
β-strand	319-323	5	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	3
β-strand	58-63	6	4
β-strand	69-74	6	4
β-strand	78-83	6	4
β-strand	88-94	7	4
β-strand	100-105	6	5
β-strand	111-116	6	5
β-strand	121-125	5	5
β-strand	134-139	6	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	218-223	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
β-strand	273-278	6	9
β-strand	284-289	6	9
β-strand	294-298	5	9
β-strand	304-308	5	9
β-strand	315-320	6	3
β-strand	327-331	5	3
β-strand	336-340	5	3

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	10
β-strand	11-12	2	11
β-strand	18-25	8	10
α-helix	29-31	3
β-strand	33-39	7	12
β-strand	45-51	7	12
β-strand	58-60	3	12
β-strand	68-73	6	10
β-strand	78-83	6	10
α-helix	88-90	3
β-strand	92-99	8	12
β-strand	110-111	2	12
β-strand	115-117	3	12
β-strand	118-119	2	11
α-helix	138-139	2
β-strand	140-141	2	13
β-strand	146-148	3	14
β-strand	155-161	7	13
β-strand	166	1	15
β-strand	172	1	15
β-strand	174-179	6	14
β-strand	186-190	5	14
β-strand	194-195	2	14
α-helix	196	1
β-strand	203-208	6	13
β-strand	211-216	6	13
β-strand	226-231	6	14
α-helix	237	1
β-strand	239	1	14
β-strand	243-246	4	14

Chain R: 14 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	104-136	33
α-helix	139-145	7
α-helix	149-178	30
α-helix	183-184	2
α-helix	197-203	7
α-helix	204-208	5
α-helix	209-235	27
α-helix	344-384	41
α-helix	391-415	25
α-helix	417-426	10

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(i) subunit alpha-1	A	protein	354	Homo sapiens	P63096 (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

>8YN6_1 Guanine nucleotide-binding protein G(i) subunit alpha-1 (chains A)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKNTIVKQMKIIHEAG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TTGIVETHFTFKDLHFKMFDVGAQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEM
NRMHASMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAA
AYIQCQFEDLNKRKDTKEIYTHFTCSTDTKNVQFVFDAVTDVIIKNNLKDCGLF

Sequence of entity 2 (B), FASTA

>8YN6_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

>8YN6_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains C)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (E), FASTA

>8YN6_4 Antibody fragment scFv16 (chains E)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELLEENLYFQ

Sequence of entity 5 (R), FASTA

>8YN6_5 Histamine H3 receptor (chains R)
DYKDDDDHHHHHHHHGQPGNGSAFLLAPNGSHAPDHNVTQQRDEENLYFQGVDMERAPPD
GPLNASGALAGEAAAAGGARGFSAAWTAVLAALMALLIVATVLGNALVMLAFVADSSLRT
QNNFFLLNLAISDFLVGAFCIPLYVPYVLTGRWTFGRGLCKLWLVVDYLLCTSSAFNIVL
ISYDRFLSVTRAVSYRAQQGDTRRAVRKMLLVWVLAFLLYGPAILSWEYLSGGSSIPEGH
CYAEFFYNWYFLITASTLEFFTPFLSVTFFNLSIYLNIQRRTRLRLDGAREAAGPEPPPE
AQPSPPPPPGCWGCWQKGHGEAMPLHRYGVGEAAVGAEAGEATLGGGGGGGSVASPTSSS
GSSSRGTERPRSLKRGSKPSASSASLEKRMKMVSQSFTQRFRLSRDRKVAKSLAVIVSIF
GLCWAPYTLLMIIRAACHGHCVPDYWYETSFWLLWANSAVNPVLYPLCHHSFRRAFTKLL
CPQKLKIQPHSSLEHCWKAAAVFTLEDFVGDWEQTAAYNLDQVLEQGGVSSLLQNLAVSV
TPIQRIVRSGENALKIDIHVIIPYEGLSADQMAQIEEVFKVVYPVDDHHFKVILPYGTLV
IDGVTPNMLNYFGRPYEGIAVFDGKKITVTGTLWNGNKIIDERLITPDGSMLFRVTINS

Ligands and cofactors

ID	Name	Formula	Copies
ITF	2-(1~{H}-imidazol-5-yl)ethyl carbamimidothioate	C6 H10 N4 S	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 P63096 (AlphaFold model), which also has an AlphaFold model), best resolution first:

6CRK 2.0 Å, Heterotrimeric G-protein in complex with an antibody fragment
3UMR 2.04 Å, Crystal structure of the G202D mutant of human G-alpha-i1
9P7Z 2.1 Å, NTSR1-Gi-NTS(8-13) Complex in the Canonical, AHD Open State (C-Open-Apo)
2OM2 2.2 Å, Crystal Structure Of Human G[alpha]i1 Bound To The Goloco Motif Of Rgs14
8YN9 2.3 Å, Cryo-EM structure of histamine H4 receptor in complex with histamine and Gi
9HYI 2.3 Å, DP81-bound serotonin 5-HT1A receptor - Gi Protein Complex
9O36 2.3 Å, CryoEM structure of mu-opioid receptor - Gi protein complex bound to fluornitrazene (FNZ)
9P80 2.3 Å, NTSR1-Gi-NTS(8-13) Complex in the Non-Canonical, AHD Open State (NC-Open-Apo)
8XXV 2.33 Å, Cryo-EM Structure of the Prostaglandin D2 Receptor 2-indomethacin Coupled to G Protein
3UMS 2.34 Å, Crystal structure of the G202A mutant of human G-alpha-i1
3ONW 2.38 Å, Structure of a G-alpha-i1 mutant with enhanced affinity for the RGS14 GoLoco motif.
20ZG 2.4 Å, Cryo-EM structure of the human neurotensin receptor 1 (hNTSR1)-Gi1 complex in the…

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