8POK: Histamine H2 receptor

Cryo-EM structure of cell-free synthesized human histamine H2 receptor coupled to heterotrimeric Gs protein in lipid environment. Determined by electron microscopy at 3.4 Å resolution. Released 6 Mar 2024.

Method: Electron microscopy
Resolution: 3.4 Å
Organisms: Homo sapiens, Lama glama
Chains: 5
Atoms: 8,042
Mol. weight: 146.87 kDa
Ligands: HSM
Released: 6 Mar 2024

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

Secondary structure: helices and β-sheets

8POK contains 30 α-helices and 49 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: 15 helices, 0 β-strands

Element	Residues	Length
α-helix	21-50	30
α-helix	58-60	3
α-helix	61-67	7
α-helix	71-72	2
α-helix	73-77	5
α-helix	78-86	9
α-helix	94-127	34
α-helix	132-135	4
α-helix	138-160	23
α-helix	188-192	5
α-helix	194-198	5
α-helix	199-215	17
α-helix	217-223	7
α-helix	238-265	28
α-helix	276-295	20

Chain B: 7 helices, 9 β-strands

Element	Residues	Length	Sheet
α-helix	10-38	29
β-strand	40-46	7	1
β-strand	195-196	2	1
β-strand	199-200	2	1
β-strand	203-209	7	1
α-helix	220-223	4
β-strand	229-233	5	1
α-helix	252-263	12
β-strand	272-276	5	1
β-strand	277	1	2
α-helix	284-286	3
α-helix	299-301	3
α-helix	318-336	19
β-strand	345-346	2	1
β-strand	349	1	2
α-helix	358-376	19

Chain C: 3 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	8-30	23
α-helix	35-39	5
α-helix	43-47	5
β-strand	54-56	3	3
β-strand	63-68	6	4
β-strand	74-79	6	4
β-strand	83-88	6	4
β-strand	93-99	7	4
β-strand	105-108	4	5
β-strand	116-121	6	5
β-strand	126-130	5	5
β-strand	139-144	6	5
β-strand	151-158	8	6
β-strand	161-166	6	6
β-strand	170-175	6	6
β-strand	181-185	5	6
β-strand	192-197	6	7
β-strand	203-208	6	7
β-strand	212-217	6	7
β-strand	226-228	3	7
β-strand	234-239	6	8
β-strand	245-250	6	8
β-strand	254-259	6	8
β-strand	265-269	5	8
β-strand	281-283	3	9
β-strand	290-293	4	9
β-strand	299-301	3	9
β-strand	311-313	3	9
β-strand	320-325	6	3
β-strand	332-336	5	3
β-strand	341-344	4	3

Chain D: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	5-21	17
α-helix	22-24	3
α-helix	30-43	14
α-helix	53-55	3

Chain E: 1 helix, 12 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	10
β-strand	11-12	2	11
β-strand	19-25	7	10
α-helix	29-31	3
β-strand	34-39	6	12
β-strand	45-51	7	12
β-strand	58-60	3	12
β-strand	69-73	5	10
β-strand	78-82	5	10
β-strand	93-98	6	12
β-strand	120	1	10
β-strand	122-123	2	12
β-strand	125-126	2	11

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Histamine H2 receptor	A	protein	375	Homo sapiens	P25021 (AlphaFold model)
Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short	B	protein	380	Homo sapiens	P63092 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	C	protein	345	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	D	protein	68	Homo sapiens	P59768 (AlphaFold model)
Nanobody35	E	protein	138	Lama glama

Sequence of entity 1 (A), FASTA

>8POK_1 Histamine H2 receptor (chains A)
KPYDGPMAPNGTASSFCLDSTACKITITVVLAVLILITVAGNVVVCLAVGLNRRLRNLTN
CFIVSLAITDLLLGLLVLPFSAIYQLSCKWSFGKVFCNIYTSLDVMLCTASILNLFMISL
DRYCAVMDPLRYPVLVTPVRVAISLVLIWVISITLSFLSIHLGWNSRNETSKGNHTTSKC
KVQVNEVYGLVDGLVTFYLPLLIMCITYYRIFKVARDQAKRINHISSWKAATIREHKATV
TLAAVMGAFIICWFPYFTAFVYRGLRGDDAINEVLEAIVLWLGYANSALNPILYAALNRD
FRTGYQQLFCCRLANRNSHKTSLRSNASQLSRTQSREPRQQEEKPLKLQVWSGTEVTAPQ
GATDRGTWSHPQFEK

Sequence of entity 2 (B), FASTA

>8POK_2 Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains B)
MGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGAGESGKSTIVKQM
RILHVNGFNGDSEKATKVQDIKNNLKEAIETIVAAMSNLVPPVELANPENQFRVDYILSV
MNVPDFDFPPEFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLDKIDVIKQADYVPSD
QDLLRCRVLTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTAIIFVVASSSYN
MVIREDNQTNRLQEALNLFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPE
FARYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCAVDTENIRR
VFNDCRDIIQRMHLRQYELL

Sequence of entity 3 (C), FASTA

>8POK_3 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains C)
GPGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHL
AKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACG
GLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQ
QTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFF
PNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCN
VWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 4 (D), FASTA

>8POK_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains D)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFC

Sequence of entity 5 (E), FASTA

>8POK_5 Nanobody35 (chains E)
QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASISY
TGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRGQ
GTQVTVSSHHHHHHEPEA

Ligands and cofactors

ID	Name	Formula	Copies
HSM	Histamine	C5 H9 N3	1

Primary citation

Cryo-EM structure of cell-free synthesized human histamine 2 receptor/G s complex in nanodisc environment. Kock, Z., Schnelle, K., Persechino, M. et al. Nat Commun (2024) 15:1831-1831. DOI 10.1038/s41467-024-46096-z · PubMed

Other PDB entries of the same protein (UniProt P25021 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8YN3 2.56 Å, Cryo-EM structure of histamine H2 receptor in complex with histamine and miniGs
8YUT 2.7 Å, Cryo-EM structure of the amthamine-bound H2R-Gs complex
9IXJ 2.92 Å, histamine-bound H2R in complex with Gs
8YN4 2.97 Å, Cryo-EM structure of histamine H2 receptor in complex with histamine and miniGq
7UL3 3.0 Å, CryoEM Structure of Inactive H2R Bound to Famotidine, Nb6M, and NabFab

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