8YUT: Amthamine-bound H2R-Gs complex

Cryo-EM structure of the amthamine-bound H2R-Gs complex. Determined by electron microscopy at 2.7 Å resolution. Released 5 Jun 2024.

Method: Electron microscopy
Resolution: 2.7 Å
Organisms: Homo sapiens, synthetic construct
Chains: 5
Atoms: 8,229
Mol. weight: 151.77 kDa
Ligands: A1D67, CLR
Released: 5 Jun 2024

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

Secondary structure: helices and β-sheets

8YUT contains 38 α-helices and 45 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: 9 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	12-38	27
β-strand	40-46	7	1
α-helix	53-59	7
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	265-277	13
β-strand	286-292	7	1
α-helix	294-301	8
α-helix	308-310	3
α-helix	313-317	5
α-helix	332-349	18
β-strand	359-363	5	1
α-helix	371-390	20

Chain B: 4 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	4-24	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	89-94	6	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	146-153	8	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	249-254	6	7
β-strand	259-265	7	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	317-320	4	2
β-strand	327-330	4	2
β-strand	336-339	4	2

Chain G: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	7-23	17
α-helix	30-43	14
α-helix	45-47	3

Chain N: 2 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	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: 20 helices, 0 β-strands

Element	Residues	Length
α-helix	14-45	32
α-helix	47-49	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	180-187	8
α-helix	188-192	5
α-helix	193-219	27
α-helix	229-260	32
α-helix	262-264	3
α-helix	267-279	13
α-helix	280-282	3
α-helix	284	1
α-helix	285-290	6
α-helix	293-304	12

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short	A	protein	378	Homo sapiens	P63092 (AlphaFold model), P63096 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	356	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)
Nanobody-35	N	protein	128	synthetic construct
Histamine H2 receptor	R	protein	411	Homo sapiens	P25021

Sequence of entity 1 (A), FASTA

>8YUT_1 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains A)
MGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGAGESGKSTIVKQM
RILHVNGYSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGA
AEEGFMTAELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQD
VLRTRVKTSGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFNDVTAIIFVVASSSYNMV
IREDNQTNRLQEALNLFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFA
RYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCSVDTENIRRVF
NDCRDIIQRMHLRQYELL

Sequence of entity 2 (B), FASTA

>8YUT_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MHHHHLEVLFQGPGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQ
MRTRRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCA
YAPSGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDT
TCALWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTG
HESDINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRL
LLAGYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (G), FASTA

>8YUT_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (N), FASTA

>8YUT_4 Nanobody-35 (chains N)
QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASISY
TGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRGQ
GTQVTVSS

Sequence of entity 5 (R), FASTA

>8YUT_5 Histamine H2 receptor (chains R)
MKTIIALSYIFCLVFADYKDDDDKEFLEVLFQGPAPNGTASSFCLDSTACKITITVVLAV
LILITVAGNVVVCLAVGLNRRLRNLTNCFIVSLAITDLLLGLLVLPFSAIYQLSCKWSFG
KVFCNIYTSLDVMLCTASILNLFMISLDRYCAVMDPLRYPVLVTPVRVAISLVLIWVISI
TLSFLSIHLGWNSRNETSKGNHTTSKCKVQVNEVYGLVDGLVTFYLPLLIMCITYYRIFK
VARDQAKRINHISSWKAATIREHKATVTLAAVMGAFIICWFPYFTAFVYRGLRGDDAINE
VLEAIVLWLGYANSALNPILYAALNRDFRTGYQQLFCCRLANRNSHKTSLRSNASQLSRT
QSREPRQQEEKPLKLQVWSGTEVTAPQGATDRLEENLYFQGHHHHHHHHHH

Ligands and cofactors

ID	Name	Formula	Copies
A1D67	5-(2-azanylethyl)-4-methyl-1,3-thiazol-2-amine	C6 H11 N3 S	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 P63092 (AlphaFold model), which also has an AlphaFold model), best resolution first:

7BPH 1.57 Å, Crystal structure of GppNHp-bound GNAS in complex with the cyclic peptide inhibitor GN13
6AU6 1.7 Å, Crystal structure of GDP-bound human GNAS R201C mutant
8F0K 1.9 Å, Human Amylin3 Receptor in complex with Gs and Pramlintide analogue peptide San385
7E5E 1.95 Å, Crystal structure of GDP-bound GNAS in complex with the cyclic peptide inhibitor GD20
7MBX 1.95 Å, Human Cholecystokinin 1 receptor (CCK1R) Gs complex
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
7RTB 2.14 Å, Peptide-19 bound to the Glucagon-Like Peptide-1 Receptor (GLP-1R)

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