8J6R: MK-6892-bound human HCAR2-Gi1 complex

Cryo-EM structure of the MK-6892-bound human HCAR2-Gi1 complex. Determined by electron microscopy at 2.76 Å resolution. Released 6 Dec 2023.

Method: Electron microscopy
Resolution: 2.76 Å
Organisms: Homo sapiens, synthetic construct
Chains: 5
Atoms: 9,120
Mol. weight: 145.47 kDa
Ligands: NAG, FI7
Released: 6 Dec 2023

Explore 8J6R in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8J6R contains 34 α-helices and 63 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, 8 β-strands

Element	Residues	Length	Sheet
α-helix	7-30	24
β-strand	34-40	7	1
α-helix	46-51	6
β-strand	185-190	6	1
β-strand	195-200	6	1
α-helix	208-210	3
α-helix	212-215	4
β-strand	220-226	7	1
β-strand	233	1	2
β-strand	241	1	2
α-helix	242-254	13
β-strand	263-269	7	1
α-helix	271-277	7
α-helix	283-285	3
α-helix	296-308	13
β-strand	319-323	5	1
α-helix	331-351	21

Chain B: 2 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	4-24	21
α-helix	30-34	5
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
β-strand	100-105	6	5
β-strand	111-116	6	5
β-strand	121-125	5	5
β-strand	134-139	6	5
β-strand	146-151	6	6
β-strand	156-161	6	6
β-strand	165-170	6	6
β-strand	175-181	7	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	250-254	5	8
β-strand	259-264	6	8
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 G: 5 helices, 0 β-strands

Element	Residues	Length
α-helix	8-23	16
α-helix	30-43	14
α-helix	45-47	3
α-helix	53-55	3
α-helix	56-58	3

Chain R: 13 helices, 4 β-strands

Element	Residues	Length	Sheet
β-strand	10-11	2	15
β-strand	18-19	2	15
α-helix	24-50	27
α-helix	51-55	5
α-helix	61-77	17
α-helix	80-88	9
α-helix	97-129	33
α-helix	135-138	4
α-helix	141-159	19
α-helix	160-162	3
β-strand	169-170	2	16
β-strand	175-176	2	16
α-helix	188-217	30
α-helix	220-222	3
α-helix	224-260	37
α-helix	266-268	3
α-helix	270-294	25

Chain S: 5 helices, 23 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	33-40	8	11
β-strand	44-51	8	11
α-helix	53-55	3
β-strand	58-60	3	11
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
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	186-189	4	13
β-strand	195	1	13
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	243-246	4	13

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(i) subunit alpha-1	A	protein	352	Homo sapiens	P63096 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	339	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	58	Homo sapiens	P59768 (AlphaFold model)
single Fab chain (scFv16)	S	protein	250	synthetic construct
Hydroxycarboxylic acid receptor 2	R	protein	295	Homo sapiens	Q8TDS4 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8J6R_1 Guanine nucleotide-binding protein G(i) subunit alpha-1 (chains A)
CTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKNTIVKQMKIIHEAGYS
EEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMTAE
LAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVKTT
GIVETHFTFKDLHFKMFDVGAQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEMNR
MHASMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAAAY
IQCQFEDLNKRKDTKEIYTHFTCSTDTKNVQFVFDAVTDVIIKNNLKDCGLF

Sequence of entity 2 (B), FASTA

>8J6R_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
SELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHLAKIYAM
HWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACGGLDNIC
SIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQQTTTFT
GHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFFPNGNAF
ATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCNVWDALK
ADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (G), FASTA

>8J6R_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
NTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENPFR

Sequence of entity 4 (S), FASTA

>8J6R_4 single Fab chain (scFv16) (chains S)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELKGS

Sequence of entity 5 (R), FASTA

>8J6R_5 Hydroxycarboxylic acid receptor 2 (chains R)
DHFLEIDKKNCCVFRDDFIVKVLPPVLGLEFIFGLLGNGLALWIFCFHLKSWKSSRIFLF
NLAVADFLLIICLPFLMDNYVRRWDWKFGDIPCRLMLFMLAMNRQGSIIFLTVVAVDRYF
RVVHPHHALNKISNRTAAIISCLLWGITIGLTVHLLKKKMPIQNGGANLCSSFSICHTFQ
WHEAMFLLEFFLPLGIILFCSARIIWSLRQRQMDRHAKIKRAITFIMVVAIVFVICFLPS
VVVRIRIFWLLHTSGTQNCEVYRSVDLAFFITLSFTYMNSMLDPVVYYFSSPSFN

Ligands and cofactors

ID	Name	Formula	Copies
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	1
FI7	2-[[2,2-dimethyl-3-[3-(5-oxidanylpyridin-2-yl)-1,2,4-oxadiazol-5-yl]propanoyl]a…	C19 H22 N4 O5	1

Primary citation

Orthosteric and allosteric modulation of human HCAR2 signaling complex. Mao, C., Gao, M., Zang, S.K. et al. Nat Commun (2023) 14:7620-7620. DOI 10.1038/s41467-023-43537-z · PubMed

Other PDB entries of the same protein (UniProt P63096 (AlphaFold model), which also has an AlphaFold model), best resolution first:

6CRK 2.0 Å, Heterotrimeric G-protein in complex with an antibody fragment
3UMR 2.04 Å, Crystal structure of the G202D mutant of human G-alpha-i1
9P7Z 2.1 Å, NTSR1-Gi-NTS(8-13) Complex in the Canonical, AHD Open State (C-Open-Apo)
2OM2 2.2 Å, Crystal Structure Of Human G[alpha]i1 Bound To The Goloco Motif Of Rgs14
8YN9 2.3 Å, Cryo-EM structure of histamine H4 receptor in complex with histamine and Gi
9HYI 2.3 Å, DP81-bound serotonin 5-HT1A receptor - Gi Protein Complex
9O36 2.3 Å, CryoEM structure of mu-opioid receptor - Gi protein complex bound to fluornitrazene (FNZ)
9P80 2.3 Å, NTSR1-Gi-NTS(8-13) Complex in the Non-Canonical, AHD Open State (NC-Open-Apo)
8XXV 2.33 Å, Cryo-EM Structure of the Prostaglandin D2 Receptor 2-indomethacin Coupled to G Protein
3UMS 2.34 Å, Crystal structure of the G202A mutant of human G-alpha-i1
3ONW 2.38 Å, Structure of a G-alpha-i1 mutant with enhanced affinity for the RGS14 GoLoco motif.
20ZG 2.4 Å, Cryo-EM structure of the human neurotensin receptor 1 (hNTSR1)-Gi1 complex in the…

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