8YN3: Histamine H2 receptor

Cryo-EM structure of histamine H2 receptor in complex with histamine and miniGs. Determined by electron microscopy at 2.56 Å resolution. Released 9 Oct 2024.

Method: Electron microscopy
Resolution: 2.56 Å
Organisms: synthetic construct, Homo sapiens
Chains: 5
Atoms: 8,201
Mol. weight: 155.86 kDa
Ligands: CLR, HSM
Released: 9 Oct 2024

Explore 8YN3 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8YN3 contains 38 α-helices and 46 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, 7 β-strands

Element	Residues	Length	Sheet
α-helix	10-39	30
β-strand	41-47	7	1
α-helix	53-55	3
β-strand	63-66	4	1
β-strand	207-214	8	1
β-strand	217-224	8	1
α-helix	234-238	5
β-strand	243-249	7	1
α-helix	266-278	13
α-helix	280-282	3
β-strand	286-292	7	1
α-helix	294-303	10
α-helix	308-311	4
α-helix	313-317	5
α-helix	326-327	2
α-helix	332-351	20
β-strand	359-363	5	1
α-helix	371-390	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 N: 2 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	3-8	6	9
β-strand	10-11	2	10
β-strand	18-25	8	9
α-helix	29-31	3
β-strand	34-39	6	10
β-strand	45-51	7	10
β-strand	58-60	3	10
β-strand	68-73	6	9
β-strand	78-83	6	9
α-helix	88-90	3
β-strand	92-98	7	10
β-strand	118	1	10
β-strand	122-125	4	10

Chain R: 18 helices, 0 β-strands

Element	Residues	Length
α-helix	15-45	31
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	193-217	25
α-helix	231-260	30
α-helix	267-285	19
α-helix	286-290	5
α-helix	293-301	9

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Engineered guanine nucleotide,binding protein G(s) 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)
Nanobody Nb35	N	protein	138	synthetic construct
Histamine H2 receptor	R	protein	568	Homo sapiens	P25021 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8YN3_1 Engineered guanine nucleotide,binding protein G(s) subunit alpha (chains A)
MGCLGNSKTEDQRNEEKAQREANKMIEKQLQKDKQVYRATHRLLLLGADNSGKSTIVKQM
RIYHVNSGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFNDVTAIIFVVDSSDYNRLQE
ALNDFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEP
GEDPRVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCSVDTENARRIFNDCRDIIQRMHL
RQYELL

Sequence of entity 2 (B), FASTA

>8YN3_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

>8YN3_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains C)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (N), FASTA

>8YN3_4 Nanobody Nb35 (chains N)
QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASISY
TGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRGQ
GTQVTVSSHHHHHHEPEA

Sequence of entity 5 (R), FASTA

>8YN3_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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