9V81: HEP-50768-bound MRGPRX4-Gq complex

cryoEM structure of HEP-50768-bound MRGPRX4-Gq complex. Determined by electron microscopy at 2.63 Å resolution. Released 6 May 2026.

Method: Electron microscopy
Resolution: 2.63 Å
Organisms: Homo sapiens, Mus musculus, Escherichia coli
Chains: 5
Atoms: 8,139
Mol. weight: 157.78 kDa
Ligands: A1L9Y
Released: 6 May 2026

Explore 9V81 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9V81 contains 38 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 B: 10 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	7-31	25
β-strand	33-39	7	1
α-helix	46-48	3
β-strand	69-76	8	1
β-strand	79-86	8	1
α-helix	96-100	5
β-strand	105-111	7	1
α-helix	118-129	12
α-helix	132-134	3
β-strand	138-144	7	1
α-helix	146-155	10
α-helix	160-163	4
α-helix	166-169	4
α-helix	184-203	20
β-strand	211-215	5	1
α-helix	223-242	20

Chain C: 3 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	4-25	22
α-helix	30-34	5
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	165-170	6	5
β-strand	176-181	6	5
β-strand	187-192	6	6
β-strand	198-203	6	6
β-strand	208-212	5	6
β-strand	218-222	5	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
α-helix	272	1
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 D: 5 helices, 0 β-strands

Element	Residues	Length
α-helix	13-23	11
α-helix	30-43	14
α-helix	45-47	3
α-helix	53-55	3
α-helix	56-58	3

Chain E: 5 helices, 24 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	9
β-strand	11-12	2	10
β-strand	19-25	7	9
α-helix	29-31	3
β-strand	33-39	7	11
β-strand	45-51	7	11
α-helix	53-55	3
β-strand	58-60	3	11
β-strand	69-73	5	9
β-strand	78-82	5	9
α-helix	88-90	3
β-strand	92-99	8	11
β-strand	111-117	7	11
β-strand	118-119	2	10
β-strand	129	1	12
β-strand	134-136	3	13
β-strand	143-148	6	12
β-strand	154	1	14
β-strand	160	1	14
β-strand	162-167	6	13
β-strand	173-178	6	13
β-strand	182-183	2	13
α-helix	184	1
β-strand	191-196	6	12
β-strand	199-204	6	12
β-strand	214-219	6	13
α-helix	225	1
β-strand	227	1	13
β-strand	232-234	3	13

Chain R: 15 helices, 0 β-strands

Element	Residues	Length
α-helix	24-50	27
α-helix	51-55	5
α-helix	60-82	23
α-helix	84-87	4
α-helix	92-125	34
α-helix	127-128	2
α-helix	129-133	5
α-helix	138-157	20
α-helix	179-203	25
α-helix	211-223	13
α-helix	224-229	6
α-helix	230-241	12
α-helix	246-249	4
α-helix	251-269	19
α-helix	270-274	5

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Gs-mini-Gq chimera	B	protein	246	Homo sapiens
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	C	protein	358	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	D	protein	71	Homo sapiens	P59768 (AlphaFold model)
scFv16	E	protein	267	Mus musculus
Soluble cytochrome b562,Mas-related G-protein coupled receptor member X4	R	protein	472	Escherichia coli, Homo sapiens	P0ABE7 (AlphaFold model), Q96LA9 (AlphaFold model)

Sequence of entity 1 (B), FASTA

>9V81_1 Gs-mini-Gq chimera (chains B)
MGSTVSAEDKAAAERSKMIDKNLREDGEKARRTLRLLLLGADNSGKSTIVKQMRILHGGS
GGSGGTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTAIIFVVDSSDYNRLQE
ALNDFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEP
GEDPRVTRAKYFIRKEFVDISTASGDGRHICYPHFTCAVDTENARRIFNDCKDIILQMNL
REYNLV

Sequence of entity 2 (C), FASTA

>9V81_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains C)
MHHHHHHLEVLFQGPGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGR
IQMRTRRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMT
CAYAPSGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSG
DTTCALWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTF
TGHESDINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSG
RLLLAGYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (D), FASTA

>9V81_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains D)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (E), FASTA

>9V81_4 scFv16 (chains E)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELKAAALEVLFQGPHHHHHHHH

Sequence of entity 5 (R), FASTA

>9V81_5 Soluble cytochrome b562,Mas-related G-protein coupled receptor member X4 (chains R)
DYKDDDDAKLQTMHHHHHHHHHHENLYFQGGTTMADLEDNWETLNDNLKVIEKADNAAQV
KDALTKMRAAALDAQKATPPKLEDKSPDSPEMKDFRHGFDILVGQIDDALKLANEGKVKE
AQAAAEQLKTTRNAYIQKYLGSTLEVLFQGPDPTVPVFGTKLTPINGREETPCYNQTLSF
TVLTCIISLVGLTGNAVVLWLLGYRMRRNAVSIYILNLAAADFLFLSFQIIRSPLRLINI
SHLIRKILVSVMTFPYFTGLSMLSAISTERCLSVLWPIWYRCRRPTHLSAVVCVLLWGLS
LLFSMLEWRFCDFLFSGADSSWCETSDFIPVAWLIFLCVVLCVSSLVLLVRILCGSRKMP
LTRLYVTILLTVLVFLLCGLPFGILGALIYRMHLNLEVLYCHVYLVCMSLSSLNSSANPI
IYFFVGSFRQRQNRQNLKLVLQRALQDKPEVDKGEGQLPEESLELSGSRLGP

Ligands and cofactors

ID	Name	Formula	Copies
A1L9Y	5-[2-fluoranyl-3-[(2S)-5-(trifluoromethyl)-2,3-dihydro-1-benzofuran-2-yl]phenyl…	C16 H10 F4 N4 O	1

Primary citation

Development of a clinically viable MRGPRX4 inverse agonist for cholestatic itch treatment. Yang, J., Shen, R., Wang, C. et al. Nat Chem Biol (2026). DOI 10.1038/s41589-026-02195-0 · PubMed

Other PDB entries of the same protein (UniProt P62873 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8QEH 1.43 Å, Crystal structure of the G11 protein heterotrimer bound to FR900359 inhibitor
8QEG 1.7 Å, Crystal structure of the G11 protein heterotrimer bound to YM-254890 inhibitor
8F0K 1.9 Å, Human Amylin3 Receptor in complex with Gs and Pramlintide analogue peptide San385
9YDQ 1.94 Å, Human delta opioid receptor complex with mini-Gi and agonist DADLE and allosteric…
9YDP 1.95 Å, Human delta opioid receptor complex with mini-Gi and agonist DADLE
6CRK 2.0 Å, Heterotrimeric G-protein in complex with an antibody fragment
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

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