9L42: Human histamine receptor H4R

Cryo-EM structure of human histamine receptor H4R in complex with agonist histamine and Gi proteins. Determined by electron microscopy at 2.9 Å resolution. Released 22 Oct 2025.

Method: Electron microscopy
Resolution: 2.9 Å
Organisms: Homo sapiens, synthetic construct
Chains: 5
Atoms: 8,762
Mol. weight: 156.64 kDa
Ligands: HSM, CLR
Released: 22 Oct 2025

Explore 9L42 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9L42 contains 40 α-helices and 65 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: 17 helices, 0 β-strands

Element	Residues	Length
α-helix	17-42	26
α-helix	49-63	15
α-helix	64-68	5
α-helix	69-76	8
α-helix	86-117	32
α-helix	119-124	6
α-helix	129-153	25
α-helix	167-170	4
α-helix	172-179	8
α-helix	180-184	5
α-helix	185-202	18
α-helix	292-325	34
α-helix	326-330	5
α-helix	338-355	18
α-helix	356-360	5
α-helix	361	1
α-helix	363-372	10

Chain B: 10 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	7-30	24
β-strand	34-40	7	1
α-helix	46-52	7
β-strand	185-191	7	1
β-strand	194-200	7	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
β-strand	263-269	7	1
α-helix	271-278	8
α-helix	283-285	3
α-helix	296-308	13
β-strand	319-323	5	1
α-helix	330-350	21

Chain C: 3 helices, 30 β-strands

Element	Residues	Length	Sheet
α-helix	4-25	22
α-helix	30-33	4
α-helix	38-41	4
β-strand	47-51	5	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	120-125	6	5
β-strand	134-140	7	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	1	7
β-strand	191-192	2	8
β-strand	198-202	5	8
β-strand	203	1	7
β-strand	208-212	5	8
β-strand	218-222	5	8
β-strand	229-234	6	9
β-strand	240-245	6	9
β-strand	250-254	5	9
β-strand	259-264	6	9
β-strand	273-278	6	10
β-strand	284-289	6	10
β-strand	294-298	5	10
β-strand	304-308	5	10
β-strand	317-320	4	3
β-strand	327-330	4	3
β-strand	336-339	4	3

Chain D: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	9-24	16
α-helix	30-43	14
α-helix	53-55	3

Chain E: 7 helices, 27 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	11
β-strand	11-12	2	12
β-strand	18-25	8	11
α-helix	29-31	3
β-strand	33-39	7	13
β-strand	45-51	7	13
α-helix	53-55	3
β-strand	58-60	3	13
β-strand	65	1	11
β-strand	68-73	6	11
β-strand	78-83	6	11
α-helix	88-90	3
β-strand	92-99	8	13
β-strand	110-111	2	13
β-strand	115-117	3	13
β-strand	118-119	2	12
β-strand	128-129	2	14
β-strand	135	1	15
α-helix	137-138	2
β-strand	143-149	7	14
β-strand	154	1	16
β-strand	160	1	16
β-strand	162-167	6	17
β-strand	174-178	5	17
β-strand	182-183	2	17
α-helix	184	1
β-strand	191-195	5	14
β-strand	199-204	6	14
β-strand	214-219	6	17
α-helix	225	1
β-strand	226-227	2	17
α-helix	228-230	3
β-strand	231-232	2	17
β-strand	233	1	15

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Histamine receptor H4R	A	protein	312	Homo sapiens	Q9H3N8 (AlphaFold model)
Guanine nucleotide-binding protein G(i) subunit alpha-1	B	protein	354	Homo sapiens	P63096 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	C	protein	354	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	D	protein	81	Homo sapiens	P59768 (AlphaFold model)
Antibody fragment scFv16	E	protein	292	synthetic construct

Sequence of entity 1 (A), FASTA

>9L42_1 Histamine receptor H4R (chains A)
MPDTNSTINLSLSTRVTLAFFMSLVAFAIMLGNALVILAFVVDKNLRHRSSYFFLNLAIS
DFFVGVISIPLYIPHTLFEWDFGKEICVFWLTTDYLLCTASVYNIVLISYDRYLSVSNAV
SYRTQHTGVLKIVTLMVAVWVLAFLVNGPMILVSESWKDEGSECEPGFFSEWYILAITSF
LEFVIPVILVAYFNMNIYWSLWKRDHLSRCQSHPGLTALHQREHVELLRARRLAKSLAIL
LGVFAVCWAPYSLFTIVLSFYSSATGPKSVWYRIAFWLQWFNSFVNPLLYPLCHKRFQKA
FLKIFCIKKQPL

Sequence of entity 2 (B), FASTA

>9L42_2 Guanine nucleotide-binding protein G(i) subunit alpha-1 (chains B)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKNTIVKQMKIIHEAG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TTGIVETHFTFKDLHFKMFDVGAQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEM
NRMHASMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAA
AYIQCQFEDLNKRKDTKEIYTHFTCSTDTKNVQFVFDAVTDVIIKNNLKDCGLF

Sequence of entity 3 (C), FASTA

>9L42_3 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains C)
MHHHHHHHHHHGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMR
TRRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYA
PSGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTC
ALWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHE
SDINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLL
AGYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 4 (D), FASTA

>9L42_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains D)
MHHHHHHHHHHASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPL
LTPVPASENPFREKKFFCAIL

Sequence of entity 5 (E), FASTA

>9L42_5 Antibody fragment scFv16 (chains E)
MLLVNQSHQGFNKEHTSKMVSAIVLYVLLAAAAHSAFADVQLVESGGGLVQPGGSRKLSC
SASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYYADTVKGRFTISRDDPKNTLFLQ
MTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVSSGGGGSGGGGSGGGGSDIVMTQ
ATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQRPGQSPQLLIYRMSNLASGVPDR
FSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFGAGTKLELKENLYFQ

Ligands and cofactors

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

Primary citation

Cryo-EM Structures and AlphaFold3 Models of Histamine Receptors Reveal Diverse Ligand Binding and G Protein Bias. Chen, A., Su, C., Zhang, Z. et al. Pharmaceuticals (Basel) (2025) 18. DOI 10.3390/ph18030292 · PubMed

Other PDB entries of the same protein (UniProt Q9H3N8 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8YN9 2.3 Å, Cryo-EM structure of histamine H4 receptor in complex with histamine and Gi
9JED 2.58 Å, Cryo-EM structure of Histamine-bound Histamine receptor 4 H4R G protein complex
8YNA 2.63 Å, Cryo-EM structure of histamine H4 receptor in complex with immepip and Gi
9LRC 2.84 Å, Cryo-EM structure of the histamine H4 receptor-Gi protein complex (Receptor focused)
9LRE 2.84 Å, Cryo-EM structure of the histamine H4 receptor-Gi protein complex (Overall)
7YFC 3.0 Å, Cryo-EM structure of the histamine-bound histamine H4 receptor and Gq complex
8HN8 3.0 Å, Cryo-EM structure of ligand histamine-bound Histamine H4 receptor Gi complex
8HOC 3.0 Å, Cryo-EM structure of ligand histamine-bound Histamine H4 receptor Gi complex
8JXW 3.01 Å, VUF6884-bound H4R/Gi complex
8JXX 3.06 Å, Clobenpropit-bound H4R/Gi complex
8JXT 3.07 Å, Histamine-bound H4R/Gi complex
7YFD 3.1 Å, Cryo-EM structure of the imetit-bound histamine H4 receptor and Gq complex

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