8YUU: Histamine-bound H3R-Gi complex

Cryo-EM structure of the histamine-bound H3R-Gi complex. Determined by electron microscopy at 2.7 Å resolution. Released 5 Jun 2024.

Method: Electron microscopy
Resolution: 2.7 Å
Organisms: Homo sapiens, Mus musculus
Chains: 5
Atoms: 9,037
Mol. weight: 167.61 kDa
Ligands: HSM, CLR
Released: 5 Jun 2024

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

Secondary structure: helices and β-sheets

8YUU contains 42 α-helices and 60 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	34-40	7	1
α-helix	46-53	8
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	227-231	5
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	271-278	8
α-helix	283-285	3
α-helix	296-308	13
β-strand	319-323	5	1
α-helix	331-350	20

Chain B: 4 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	3-24	22
α-helix	30-33	4
α-helix	34-36	3
α-helix	38-39	2
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	89-94	6	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	187-192	6	7
β-strand	198-203	6	7
β-strand	207-212	6	7
β-strand	217-223	7	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	293-298	6	9
β-strand	304-309	6	9
β-strand	315-320	6	3
β-strand	327-331	5	3
β-strand	336-339	4	3

Chain G: 6 helices, 0 β-strands

Element	Residues	Length
α-helix	6-23	18
α-helix	27-29	3
α-helix	30-43	14
α-helix	45-47	3
α-helix	53-55	3
α-helix	56-58	3

Chain R: 14 helices, 0 β-strands

Element	Residues	Length
α-helix	34-61	28
α-helix	68-82	15
α-helix	83-87	5
α-helix	88-97	10
α-helix	107-137	31
α-helix	139-145	7
α-helix	150-172	23
α-helix	175-178	4
α-helix	196-203	8
α-helix	204-208	5
α-helix	209-234	26
α-helix	344-383	40
α-helix	391-415	25
α-helix	417-426	10

Chain S: 7 helices, 24 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	10
β-strand	10-12	3	11
β-strand	17-25	9	10
α-helix	29-31	3
β-strand	33-39	7	11
β-strand	45-51	7	11
β-strand	58-60	3	11
α-helix	62-64	3
β-strand	68-73	6	10
β-strand	78-84	7	10
α-helix	88-90	3
β-strand	92-99	8	11
β-strand	110-111	2	11
β-strand	115-119	5	11
α-helix	138-139	2
β-strand	140-141	2	12
β-strand	146-148	3	13
β-strand	155-161	7	12
β-strand	166	1	14
β-strand	172	1	14
β-strand	174-179	6	13
β-strand	186-191	6	13
β-strand	194-195	2	13
α-helix	196	1
β-strand	203-208	6	12
β-strand	211-216	6	12
α-helix	221-223	3
β-strand	226-231	6	13
α-helix	237	1
β-strand	238-239	2	13
β-strand	243-246	4	13

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Histamine H3 receptor	R	protein	461	Homo sapiens	Q9Y5N1 (AlphaFold model)
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	358	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	71	Homo sapiens	P59768 (AlphaFold model)
scFv16	S	protein	269	Mus musculus

Sequence of entity 1 (R), FASTA

>8YUU_1 Histamine H3 receptor (chains R)
DYKDDDDKLEVLFQGPMERAPPDGPLNASGALAGEAAAAGGARGFSAAWTAVLAALMALL
IVATVLGNALVMLAFVADSSLRTQNNFFLLNLAISDFLVGAFCIPLYVPYVLTGRWTFGR
GLCKLWLVVDYLLCTSSAFNIVLISYDRFLSVTRAVSYRAQQGDTRRAVRKMLLVWVLAF
LLYGPAILSWEYLSGGSSIPEGHCYAEFFYNWYFLITASTLEFFTPFLSVTFFNLSIYLN
IQRRTRLRLDGAREAAGPEPPPEAQPSPPPPPGCWGCWQKGHGEAMPLHRYGVGEAAVGA
EAGEATLGGGGGGGSVASPTSSSGSSSRGTERPRSLKRGSKPSASSASLEKRMKMVSQSF
TQRFRLSRDRKVAKSLAVIVSIFGLCWAPYTLLMIIRAACHGHCVPDYWYETSFWLLWAN
SAVNPVLYPLCHHSFRRAFTKLLCPQKLKIQPHSSLEHCWK

Sequence of entity 2 (A), FASTA

>8YUU_2 Guanine nucleotide-binding protein G(i) subunit alpha-1 (chains A)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKNTIVKQMKIIHEAG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TTGIVETHFTFKDLHFKMFDVGAQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEM
NRMHASMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAA
AYIQCQFEDLNKRKDTKEIYTHFTCSTDTKNVQFVFDAVTDVIIKNNLKDCGLF

Sequence of entity 3 (B), FASTA

>8YUU_3 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MHHHHHHLEVLFQGPGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGR
IQMRTRRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMT
CAYAPSGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSG
DTTCALWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTF
TGHESDINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSG
RLLLAGYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 4 (G), FASTA

>8YUU_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 5 (S), FASTA

>8YUU_5 scFv16 (chains S)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELKGSLEVLFQGPAAAHHHHHHHH

Ligands and cofactors

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

Primary citation

Molecular Determinant Underlying Selective Coupling of Primary G-Protein by Class A GPCRs. Shen, Q., Tang, X., Wen, X. et al. Adv Sci (Weinh) (2024) 11:e2310120-e2310120. DOI 10.1002/advs.202310120 · PubMed

Other PDB entries of the same protein (UniProt Q9Y5N1 (AlphaFold model), which also has an AlphaFold model), best resolution first:

7F61 2.6 Å, Crystal structure of human histamine receptor H3R in complex with antagonist PF03654746
8YN5 2.7 Å, Cryo-EM structure of histamine H3 receptor in complex with histamine and Gi
8YN6 2.77 Å, Cryo-EM structure of histamine H3 receptor in complex with imetit and Gi
8YN7 2.77 Å, Cryo-EM structure of histamine H3 receptor in complex with immethridine and miniGo
8YN8 2.77 Å, Cryo-EM structure of histamine H3 receptor in complex with proxyfan and miniGo
8YUV 3.0 Å, Cryo-EM structure of the immepip-bound H3R-Gi complex
9JEQ 3.05 Å, Cryo-EM structure of Histamine-bound Histamine receptor 3 H3R G protein complex

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