9IZC: Human HCAR2-Gi complex with MK1903

Cryo-EM structure of human HCAR2-Gi complex with MK1903. Determined by electron microscopy at 2.68 Å resolution. Released 2 Apr 2025.

Method: Electron microscopy
Resolution: 2.68 Å
Organism: Homo sapiens
Chains: 5
Atoms: 8,986
Mol. weight: 144.28 kDa
Ligands: XOT
Released: 2 Apr 2025

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

Secondary structure: helices and β-sheets

9IZC contains 33 α-helices and 64 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, 4 β-strands

Element	Residues	Length	Sheet
β-strand	10-11	2	1
β-strand	18-19	2	1
α-helix	30-54	25
α-helix	61-78	18
α-helix	80-88	9
α-helix	97-130	34
α-helix	135-138	4
α-helix	141-157	17
α-helix	160-162	3
β-strand	169-170	2	2
β-strand	175-176	2	2
α-helix	188-217	30
α-helix	224-260	37
α-helix	270-294	25

Chain B: 5 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	6-25	20
α-helix	30-33	4
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	88-94	7	4
α-helix	95	1
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	208-212	5	7
β-strand	218-222	5	7
β-strand	229-234	6	8
β-strand	240-245	6	8
β-strand	249-254	6	8
β-strand	259-265	7	8
α-helix	272	1
β-strand	273-278	6	9
β-strand	284-289	6	9
β-strand	294-298	5	9
β-strand	304-308	5	9
β-strand	315-320	6	3
β-strand	327-331	5	3
β-strand	336-339	4	3

Chain C: 8 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	7-30	24
β-strand	33-39	7	10
α-helix	46-50	5
β-strand	185-191	7	10
β-strand	194-200	7	10
α-helix	208-211	4
α-helix	212-215	4
β-strand	220-226	7	10
α-helix	242-254	13
β-strand	263-269	7	10
α-helix	271-280	10
α-helix	296-308	13
β-strand	319-322	4	10
α-helix	330-350	21

Chain G: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	10-23	14
α-helix	30-44	15
α-helix	45-47	3
α-helix	54-55	2

Chain S: 6 helices, 26 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	11
β-strand	10-12	3	12
β-strand	19-25	7	11
α-helix	29-31	3
β-strand	33-39	7	12
β-strand	45-51	7	12
β-strand	58-60	3	12
β-strand	68-73	6	11
α-helix	74-76	3
β-strand	78-83	6	11
α-helix	88-90	3
β-strand	92-95	4	12
β-strand	98-99	2	12
β-strand	110	1	12
β-strand	115-119	5	12
α-helix	125-127	3
β-strand	128-129	2	13
β-strand	134-136	3	14
β-strand	143-147	5	15
β-strand	148-149	2	13
β-strand	154	1	16
β-strand	160	1	16
β-strand	162-167	6	14
β-strand	174-178	5	14
β-strand	182-183	2	14
α-helix	184	1
β-strand	191-196	6	15
β-strand	199-204	6	15
β-strand	213-219	7	14
α-helix	225	1
β-strand	227	1	14
β-strand	231-234	4	14

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Hydroxycarboxylic acid receptor 2	A	protein	294	Homo sapiens	Q8TDS4 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	337	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(i) subunit alpha-1	C	protein	351	Homo sapiens	P63096 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	56	Homo sapiens	P59768 (AlphaFold model)
scFv16	S	protein	248	Homo sapiens

Sequence of entity 1 (A), FASTA

>9IZC_1 Hydroxycarboxylic acid receptor 2 (chains A)
DHFLEIDKKNCCVFRDDFIVKVLPPVLGLEFIFGLLGNGLALWIFCFHLKSWKSSRIFLF
NLAVADFLLIICLPFLMDNYVRRWDWKFGDIPCRLMLFMLAMNRQGSIIFLTVVAVDRYF
RVVHPHHALNKISNRTAAIISCLLWGITIGLTVHLLKKKMPIQNGGANLCSSFSICHTFQ
WHEAMFLLEFFLPLGIILFCSARIIWSLRQRQMDRHAKIKRAITFIMVVAIVFVICFLPS
VVVRIRIFWLLHTSGTQNCEVYRSVDLAFFITLSFTYMNSMLDPVVYYFSSPSF

Sequence of entity 2 (B), FASTA

>9IZC_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
LDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHLAKIYAMHW
GTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACGGLDNICSI
YNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQQTTTFTGH
TGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFFPNGNAFAT
GSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCNVWDALKAD
RAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (C), FASTA

>9IZC_3 Guanine nucleotide-binding protein G(i) subunit alpha-1 (chains C)
TLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKSTIVKQMKIIHEAGYSE
EECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMTAEL
AGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVKTTG
IVETHFTFKDLHFKMFDVGAQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEMNRM
HESMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAAAYI
QCQFEDLNKRKDTKEIYTHFTCSTDTKNVQFVFDAVTDVIIKNNLKDCGLF

Sequence of entity 4 (G), FASTA

>9IZC_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
SIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENPFRE

Sequence of entity 5 (S), FASTA

>9IZC_5 scFv16 (chains S)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQ
RPGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTF
GAGTKLEL

Ligands and cofactors

ID	Name	Formula	Copies
XOT	(4aR,5aR)-4,4a,5,5a-tetrahydro-1H-cyclopropa[4,5]cyclopenta[1,2-c]pyrazole-3-ca…	C8 H8 N2 O2	1

Primary citation

Structures of G-protein coupled receptor HCAR1 in complex with Gi1 protein reveal the mechanistic basis for ligand recognition and agonist selectivity. Pan, X., Ye, F., Ning, P. et al. PLoS Biol (2025) 23:e3003126-e3003126. DOI 10.1371/journal.pbio.3003126 · PubMed

Other PDB entries of the same protein (UniProt Q8TDS4 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8J6P 2.55 Å, Cryo-EM structure of the MK-6892-bound human HCAR2-Gi1 complex
8J6Q 2.6 Å, Cryo-EM structure of the 3-HB and compound 9n-bound human HCAR2-Gi1 complex
8JZ7 2.6 Å, Cryo-EM structure of MK-6892-bound HCAR2 in complex with Gi protein
8IJA 2.69 Å, Cryo-EM structure of human HCAR2-Gi complex with niacin
7ZL9 2.7 Å, Crystal structure of human GPCR Niacin receptor (HCA2)
7ZLY 2.7 Å, Crystal structure of human GPCR Niacin receptor (HCA2) expressed from Spodoptera…
9JKY 2.72 Å, acifran-HCAR2-Gi complex
9KT8 2.73 Å, Cryo-EM structure of HCA2-Gi complex with acifran
8J6R 2.76 Å, Cryo-EM structure of the MK-6892-bound human HCAR2-Gi1 complex
8I7V 2.77 Å, Cryo-EM structure of Acipimox bound human hydroxy-carboxylic acid receptor 2 in complex…
8J6J 2.8 Å, Cryo-EM structure of thehydroxycarboxylic acid receptor 2-Gi protein complex bound with…
9KT7 2.8 Å, Cryo-EM structure of HCA2-Gi complex with MK6892

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