9LRE: Histamine H4 receptor-Gi protein complex

Cryo-EM structure of the histamine H4 receptor-Gi protein complex (Overall). Determined by electron microscopy at 2.84 Å resolution. Released 11 Jun 2025.

Method: Electron microscopy
Resolution: 2.84 Å
Organisms: Homo sapiens, Rattus norvegicus, Mus musculus
Chains: 5
Atoms: 8,845
Mol. weight: 192.33 kDa
Ligands: HSM
Released: 11 Jun 2025

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

Secondary structure: helices and β-sheets

9LRE contains 36 α-helices and 58 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, 6 β-strands

Element	Residues	Length	Sheet
α-helix	12-30	19
β-strand	33-39	7	1
α-helix	46-52	7
β-strand	185-191	7	1
β-strand	194-200	7	1
α-helix	208-211	4
α-helix	212-215	4
β-strand	220-226	7	1
α-helix	242-254	13
α-helix	257-259	3
β-strand	263-269	7	1
α-helix	271-278	8
α-helix	283-285	3
α-helix	296-308	13
β-strand	319-324	6	1
α-helix	331-350	20

Chain B: 4 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	5-25	21
α-helix	30-33	4
α-helix	34-36	3
α-helix	38-39	2
β-strand	47-51	5	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	303-308	6	8
β-strand	315-320	6	2
β-strand	327-331	5	2
β-strand	336-339	4	2

Chain E: 5 helices, 24 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	9
β-strand	10-12	3	10
β-strand	17-25	9	9
α-helix	29-31	3
β-strand	33-40	8	10
β-strand	44-51	8	10
β-strand	58-60	3	10
β-strand	69-73	5	9
β-strand	78-84	7	9
α-helix	88-90	3
β-strand	92-99	8	10
β-strand	110-111	2	10
β-strand	115-119	5	10
α-helix	125-127	3
β-strand	128-130	3	11
β-strand	134-136	3	12
β-strand	143-149	7	11
β-strand	154	1	13
β-strand	160	1	13
β-strand	162-167	6	12
β-strand	174-178	5	12
β-strand	182-183	2	12
β-strand	191-195	5	11
β-strand	199-204	6	11
α-helix	209-211	3
β-strand	214-219	6	12
α-helix	225	1
β-strand	226-227	2	12
β-strand	231-234	4	12

Chain G: 2 helices, 0 β-strands

Element	Residues	Length	Sheet
α-helix	7-24	18
α-helix	30-43	14

Chain R: 15 helices, 0 β-strands

Element	Residues	Length
α-helix	12-43	32
α-helix	49-63	15
α-helix	64-68	5
α-helix	69-76	8
α-helix	84-117	34
α-helix	119-124	6
α-helix	129-154	26
α-helix	155-157	3
α-helix	167-170	4
α-helix	172-179	8
α-helix	180-184	5
α-helix	185-204	20
α-helix	290-328	39
α-helix	338-357	20
α-helix	363-373	11

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	351	Rattus norvegicus	P54311 (AlphaFold model)
scFv16	E	protein	260	Mus musculus
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	68	Bos taurus	P63212 (AlphaFold model)
Histamine H4 receptor,Genome polyprotein	R	protein	692	Homo sapiens	Q9H3N8 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>9LRE_1 Guanine nucleotide-binding protein G(i) subunit alpha-1 (chains A)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKNTIVKQMKIIHEAG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TTGIVETHFTFKDLHFKMFDVGAQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEM
NRMHASMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAA
AYIQCQFEDLNKRKDTKEIYTHFTCSTDTKNVQFVFDAVTDVIIKNNLKDCGLF

Sequence of entity 2 (B), FASTA

>9LRE_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MHHHHHHGSLLQSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRR
TLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSG
NYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALW
DIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDI
NAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGY
DDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (E), FASTA

>9LRE_3 scFv16 (chains E)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELKAAAASSEDLYFQ

Sequence of entity 4 (G), FASTA

>9LRE_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFS

Sequence of entity 5 (R), FASTA

>9LRE_5 Histamine H4 receptor,Genome polyprotein (chains R)
MKTIIALSYIFCLVFADYKDDDDKGSGGSSGGGSPDTNSTINLSLSTRVTLAFFMSLVAF
AIMLGNALVILAFVVDKNLRHRSSYFFLNLAISDFFVGVISIPLYIPHTLFEWDFGKEIC
VFWLTTDYLLCTASVYNIVLISYDRYLSVSNAVSYRTQHTGVLKIVTLMVAVWVLAFLVN
GPMILVSESWKDEGSECEPGFFSEWYILAITSFLEFVIPVILVAYFNMNIYWSLWKRDHL
SRCQSHPGLTAVSSNICGHSFRGRLSSRRSLSASTEVPASFHSERQRRKSSLMFSSRTKM
NSNTIASKMGSFSQSDSVALHQREHVELLRARRLAKSLAILLGVFAVCWAPYSLFTIVLS
FYSSATGPKSVWYRIAFWLQWFNSFVNPLLYPLCHKRFQKAFLKIFCIKKQPLPSQHSRS
VSSGGSGGGSGGSSGGGSLEVLFQGPVSKGEELFTGVVPILVELDGDVNGHKFSVSGEGE
GDATYGKLTLKFICTTGKLPVPWPTLVTTLTYGVQCFSRYPDHMKQHDFFKSAMPEGYVQ
ERTIFFKDDGNYKTRAEVKFEGDTLVNRIELKGIDFKEDGNILGHKLEYNYNSHNVYIMA
DKQKNGIKVNFKIRHNIEDGSVQLADHYQQNTPIGDGPVLLPDNHYLSTQSKLSKDPNEK
RDHMVLLEFVTAAGITLGMDELYKHHHHHHHH

Ligands and cofactors

ID	Name	Formula	Copies
HSM	Histamine	C5 H9 N3	1

Primary citation

Structural insights into ligand recognition and G protein preferences across histamine receptors. Matsuzaki, Y., Sano, F.K., Oshima, H.S. et al. Commun Biol (2025) 8:957-957. DOI 10.1038/s42003-025-08363-7 · 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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