8YN4: Histamine H2 receptor

Cryo-EM structure of histamine H2 receptor in complex with histamine and miniGq. Determined by electron microscopy at 2.97 Å resolution. Released 9 Oct 2024.

Method: Electron microscopy
Resolution: 2.97 Å
Organisms: synthetic construct, Homo sapiens
Chains: 5
Atoms: 8,661
Mol. weight: 167.13 kDa
Ligands: CLR, HSM
Released: 9 Oct 2024

Explore 8YN4 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8YN4 contains 39 α-helices and 62 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, 9 β-strands

Element	Residues	Length	Sheet
α-helix	7-28	22
β-strand	33-39	7	1
α-helix	46-53	8
β-strand	70-75	6	1
β-strand	80-85	6	1
α-helix	96-100	5
β-strand	105-108	4	1
β-strand	109-111	3	2
α-helix	118-129	12
β-strand	138-139	2	1
β-strand	142-144	3	2
α-helix	146-155	10
α-helix	160-163	4
α-helix	165-167	3
α-helix	178-179	2
α-helix	184-203	20
β-strand	211	1	1
β-strand	214-215	2	2
α-helix	223-355	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	249-254	6	8
β-strand	259-265	7	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: 17 helices, 0 β-strands

Element	Residues	Length
α-helix	16-45	30
α-helix	52-54	3
α-helix	55-66	12
α-helix	67-71	5
α-helix	72-81	10
α-helix	88-121	34
α-helix	126-129	4
α-helix	132-147	16
α-helix	148-152	5
α-helix	153-155	3
α-helix	175-177	3
α-helix	180-186	7
α-helix	187-192	6
α-helix	193-215	23
α-helix	231-260	30
α-helix	267-287	21
α-helix	293-300	8

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Engineered guanine nucleotide-binding protein G(q) subunit alpha	A	protein	246	synthetic construct
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 H2 receptor	R	protein	568	Homo sapiens	P25021 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8YN4_1 Engineered guanine nucleotide-binding protein G(q) subunit alpha (chains A)
MGSTVSAEDKAAAERSKMIDKNLREDGEKARRTLRLLLLGADNSGKSTIVKQMRILHGGS
GGSGGTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTAIIFVVDSSDYNRLQE
ALNDFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEP
GEDPRVTRAKYFIRKEFVDISTASGDGRHICYPHFTCAVDTENARRIFNDCKDIILQMNL
REYNLV

Sequence of entity 2 (B), FASTA

>8YN4_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

>8YN4_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains C)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (E), FASTA

>8YN4_4 Antibody fragment scFv16 (chains E)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELLEENLYFQ

Sequence of entity 5 (R), FASTA

>8YN4_5 Histamine H2 receptor (chains R)
DYKDDDDHHHHHHHHGQPGNGSAFLLAPNGSHAPDHNVTQQRDEGGSGQPGNGSAFLLAP
NGSHAPDHNVTQQRDEENLYFQGVDMAPNGTASSFCLDSTACKITITVVLAVLILITVAG
NVVVCLAVGLNRRLRNLTNCFIVSLAITDLLLGLLVLPFSAIYQLSCKWSFGKVFCNIYT
SLDVMLCTASILNLFMISLDRYCAVMDPLRYPVLVTPVRVAISLVLIWVISITLSFLSIH
LGWNSRNETSKGNHTTSKCKVQVNEVYGLVDGLVTFYLPLLIMCITYYRIFKVARDQAKR
INHISSWKAATIREHKATVTLAAVMGAFIICWFPYFTAFVYRGLRGDDAINEVLEAIVLW
LGYANSALNPILYAALNRDFRTGYQQLFCCRLAHMGSSGGGGSGGGGSSGVFTLEDFVGD
WEQTAAYNLDQVLEQGGVSSLLQNLAVSVTPIQRIVRSGENALKIDIHVIIPYEGLSADQ
MAQIEEVFKVVYPVDDHHFKVILPYGTLVIDGVTPNMLNYFGRPYEGIAVFDGKKITVTG
TLWNGNKIIDERLITPDGSMLFRVTINS

Ligands and cofactors

ID	Name	Formula	Copies
CLR	Cholesterol	C27 H46 O	1
HSM	Histamine	C5 H9 N3	1

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 P62873 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8QEH 1.43 Å, Crystal structure of the G11 protein heterotrimer bound to FR900359 inhibitor
8QEG 1.7 Å, Crystal structure of the G11 protein heterotrimer bound to YM-254890 inhibitor
8F0K 1.9 Å, Human Amylin3 Receptor in complex with Gs and Pramlintide analogue peptide San385
9YDQ 1.94 Å, Human delta opioid receptor complex with mini-Gi and agonist DADLE and allosteric…
9YDP 1.95 Å, Human delta opioid receptor complex with mini-Gi and agonist DADLE
6CRK 2.0 Å, Heterotrimeric G-protein in complex with an antibody fragment
8F0J 2.0 Å, Calcitonin Receptor in complex with Gs and Pramlintide analogue peptide San45
8F2B 2.0 Å, Amylin 3 Receptor in complex with Gs and Pramlintide analogue peptide San45
9XXT 2.0 Å, Cryo-EM structure of lysophosphatidylserine (18:0)-bound GPR174-Gs complex
6X18 2.1 Å, GLP-1 peptide hormone bound to Glucagon-Like peptide-1 (GLP-1) Receptor
6X19 2.1 Å, Non peptide agonist CHU-128, bound to Glucagon-Like peptide-1 (GLP-1) Receptor
9NTU 2.1 Å, Cryo-EM structure of BETP-GLP-1(9-36)-GLP-1R-Gs complex

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