8JD3: Gi1-bound mGlu2-mGlu3 heterodimer

Cryo-EM structure of Gi1-bound mGlu2-mGlu3 heterodimer. Determined by electron microscopy at 3.3 Å resolution. Released 21 Jun 2023.

Method: Electron microscopy
Resolution: 3.3 Å
Organism: Homo sapiens
Chains: 5
Atoms: 15,770
Mol. weight: 286.01 kDa
Ligands: HZR, GLU, CLR, PEF
Released: 21 Jun 2023

Explore 8JD3 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8JD3 contains 73 α-helices and 84 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 2: 31 helices, 23 β-strands

Element	Residues	Length	Sheet
β-strand	32-38	7	1
β-strand	41	1	2
α-helix	42-43	2
β-strand	53	1	2
α-helix	54	1
α-helix	60-74	15
α-helix	82-83	2
β-strand	84-90	7	1
α-helix	95-107	13
β-strand	136-141	6	1
α-helix	145-157	13
β-strand	162-164	3	1
α-helix	170-173	4
β-strand	182-183	2	1
α-helix	188-201	14
β-strand	206-212	7	3
α-helix	217-230	14
β-strand	234-241	8	3
α-helix	247-259	13
β-strand	265-269	5	3
α-helix	272-284	13
β-strand	290-292	3	3
β-strand	315-319	5	3
α-helix	325-332	8
α-helix	343-353	11
α-helix	357-359	3
α-helix	376-378	3
α-helix	379-399	21
α-helix	408-410	3
α-helix	415-418	4
α-helix	419-423	5
β-strand	427-428	2	4
β-strand	441-442	2	4
β-strand	453-459	7	3
β-strand	467-474	8	3
β-strand	478	1	3
α-helix	494-496	3
β-strand	509-510	2	5
β-strand	523-524	2	5
β-strand	545-548	4	6
β-strand	552-554	3	6
α-helix	569-591	23
α-helix	596-599	4
α-helix	605-623	19
α-helix	629-662	34
α-helix	670-671	2
α-helix	678-700	23
β-strand	706-710	5	7
β-strand	713-720	8	7
α-helix	725-728	4
α-helix	729-746	18
α-helix	763-783	21
α-helix	789-809	21
α-helix	811-818	8

Chain 3: 27 helices, 24 β-strands

Element	Residues	Length	Sheet
β-strand	39-45	7	8
β-strand	48-51	4	9
β-strand	57-60	4	9
α-helix	62-66	5
α-helix	67-81	15
α-helix	89-90	2
β-strand	91-97	7	8
α-helix	102-109	8
β-strand	142-146	5	8
α-helix	151-161	11
β-strand	168-169	2	8
β-strand	187	1	8
α-helix	194-207	14
β-strand	212-218	7	10
α-helix	223-236	14
β-strand	240-247	8	10
α-helix	258-265	8
β-strand	271-275	5	10
α-helix	278-291	14
β-strand	296-299	4	10
β-strand	320-325	6	10
α-helix	331-338	8
α-helix	349-358	10
α-helix	390-411	22
α-helix	420-422	3
α-helix	427-428	2
α-helix	429-435	7
β-strand	439-441	3	11
α-helix	450-452	3
β-strand	453-455	3	11
β-strand	466-474	9	10
β-strand	477-486	10	10
α-helix	494-496	3
β-strand	518-521	4	12
β-strand	530-533	4	12
β-strand	538-542	5	13
β-strand	545-548	4	13
β-strand	553-554	2	14
α-helix	562	1
β-strand	563-564	2	14
α-helix	565-566	2
α-helix	575-601	27
α-helix	612-633	22
α-helix	635-636	2
α-helix	638-665	28
α-helix	685-709	25
β-strand	714-717	4	15
β-strand	727-730	4	15
α-helix	734-758	25
α-helix	768-792	25
α-helix	796-828	33

Chain A: 9 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	9-32	24
β-strand	38-40	3	16
β-strand	186-189	4	17
α-helix	191-193	3
β-strand	196-199	4	17
α-helix	208-212	5
α-helix	213-215	3
β-strand	220-224	5	16
α-helix	242-255	14
β-strand	263-267	5	16
α-helix	273-278	6
α-helix	297-307	11
α-helix	312-316	5
β-strand	319-321	3	16
α-helix	332-349	18

Chain B: 3 helices, 31 β-strands

Element	Residues	Length	Sheet
α-helix	5-35	31
β-strand	50-51	2	18
β-strand	61	1	19
β-strand	70-73	4	19
β-strand	78	1	20
β-strand	79-82	4	19
β-strand	89	1	19
β-strand	94	1	20
β-strand	100-103	4	21
β-strand	111-116	6	21
β-strand	121-125	5	21
β-strand	137	1	21
β-strand	149-151	3	22
β-strand	156-159	4	22
β-strand	167-170	4	22
β-strand	176-179	4	22
α-helix	186-187	2
β-strand	198-201	4	23
β-strand	209-212	4	23
β-strand	218-220	3	23
α-helix	228	1
β-strand	229	1	24
β-strand	240-241	2	25
β-strand	245	1	24
β-strand	251	1	26
β-strand	253-254	2	25
β-strand	263	1	26
β-strand	273-278	6	27
β-strand	285-289	5	27
β-strand	294-298	5	27
β-strand	303-308	6	27
β-strand	315-320	6	18
β-strand	327-331	5	18
β-strand	336-338	3	18

Chain C: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	10-27	18
α-helix	33-40	8
α-helix	48-51	4

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Metabotropic glutamate receptor 2	2	protein	870	Homo sapiens	Q14416 (AlphaFold model)
Metabotropic glutamate receptor 3	3	protein	894	Homo sapiens	Q14832 (AlphaFold model)
Guanine nucleotide-binding protein G(i) subunit alpha-1	A	protein	354	Homo sapiens	P63096 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	351	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	C	protein	71	Homo sapiens	P59768

Sequence of entity 1 (2), FASTA

>8JD3_1 Metabotropic glutamate receptor 2 (chains 2)
DYKDDDDGAPEGPAKKVLTLEGDLVLGGLFPVHQKGGPAEDCGPVNEHRGIQRLEAMLFA
LDRINRDPHLLPGVRLGAHILDSCSKDTHALEQALDFVRASLSRGADGSRHICPDGSYAT
HGDAPTAITGVIGGSYSDVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTVPPD
FFQAKAMAEILRFFNWTYVSTVASEGDYGETGIEAFELEARARNICVATSEKVGRAMSRA
AFEGVVRALLQKPSARVAVLFTRSEDARELLAASQRLNASFTWVASDGWGALESVVAGSE
GAAEGAITIELASYPISDFASYFQSLDPWNNSRNPWFREFWEQRFRCSFRQRDCAAHSLR
AVPFEQESKIMFVVNAVYAMAHALHNMHRALCPNTTRLCDAMRPVNGRRLYKDFVLNVKF
DAPFRPADTHNEVRFDRFGDGIGRYNIFTYLRAGSGRYRYQKVGYWAEGLTLDTSLIPWA
SPSAGPLPASRCSEPCLQNEVKSVQPGEVCCWLCIPCQPYEYRLDEFTCADCGLGYWPNA
SLTGCFELPQEYIRWGDAWAVGPVTIACLGALATLFVLGVFVRHNATPVVKASGRELCYI
LLGGVFLCYCMTFIFIAKPSTAVCTLRRLGLGTAFSVCYSALLTKTNRIARIFGGAREGA
QRPRFISPASQVAICLALISGQLLIVVAWLVVEAPGTGKETAPERREVVTLRCNHRDASM
LGSLAYNVLLIALCTLYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYR
VQTTTMCVSVSLSGSVVLGCLFAPKLHIILFQPQKNVVSHRAPTSRFGSAAARASSSLGQ
GSGSQFVPTVCNGREVVDSTTSSLLEVLFQ

Sequence of entity 2 (3), FASTA

>8JD3_2 Metabotropic glutamate receptor 3 (chains 3)
DYKDDDDKGAPWSHPQFEKGSGSWSHPQFEKLGDHNFLRREIKIEGDLVLGGLFPINEKG
TGTEECGRINEDRGIQRLEAMLFAIDEINKDDYLLPGVKLGVHILDTCSRDTYALEQSLE
FVRASLTKVDEAEYMCPDGSYAIQENIPLLIAGVIGGSYSSVSIQVANLLRLFQIPQISY
ASTSAKLSDKSRYDYFARTVPPDFYQAKAMAEILRFFNWTYVSTVASEGDYGETGIEAFE
QEARLRNICIATAEKVGRSNIRKSYDSVIRELLQKPNARVVVLFMRSDDSRELIAAASRA
NASFTWVASDGWGAQESIIKGSEHVAYGAITLELASQPVRQFDRYFQSLNPYNNHRNPWF
RDFWEQKFQCSLQNKRNHRRVCDKHLAIDSSNYEQESKIMFVVNAVYAMAHALHKMQRTL
CPNTTKLCDAMKILDGKKLYKDYLLKINFTAPFNPNKDADSIVKFDTFGDGMGRYNVFNF
QNVGGKYSYLKVGHWAETLSLDVNSIHWSRNSVPTSQCSDPCAPNEMKNMQPGDVCCWIC
IPCEPYEYLADEFTCMDCGSGQWPTADLTGCYDLPEDYIRWEDAWAIGPVTIACLGFMCT
CMVVTVFIKHNNTPLVKASGRELCYILLFGVGLSYCMTFFFIAKPSPVICALRRLGLGSS
FAICYSALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLGLILVQIVMVSVWLILEA
PGTRRYTLAEKRETVILKCNVKDSSMLISLTYDVILVILCTVYAFKTRKCPENFNEAKFI
GFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTMCISVSLSGFVVLGCLFAPKVHIILFQPQ
KNVVTHRLHLNRFSVSGTGTTYSQSSASTYVPTVCNGREVLDSTTSSLLEVLFQ

Sequence of entity 3 (A), FASTA

>8JD3_3 Guanine nucleotide-binding protein G(i) subunit alpha-1 (chains A)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKNTIVKQMKIIHEAG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TTGIVETHFTFKDLHFKMFDVGAQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEM
NRMHASMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAA
AYIQCQFEDLNKRKDTKEIYTHFTCSTDTKNVQFVFDAVTDVIIKNNLKDCGLF

Sequence of entity 4 (B), FASTA

>8JD3_4 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MHHHHHHGSLLQSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRR
TLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSG
NYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALW
DIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDI
NAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGY
DDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 5 (C), FASTA

>8JD3_5 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains C)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Ligands and cofactors

ID	Name	Formula	Copies
HZR	1-butyl-3-chloranyl-4-(4-phenylpiperidin-1-yl)pyridin-2-one	C20 H25 Cl N2 O	1
GLU	Glutamic acid	C5 H9 N O4	2
CLR	Cholesterol	C27 H46 O	3
PEF	Di-palmitoyl-3-sn-phosphatidylethanolamine	C37 H74 N O8 P	1

Primary citation

Structural insights into dimerization and activation of the mGlu2-mGlu3 and mGlu2-mGlu4 heterodimers. Wang, X., Wang, M., Xu, T. et al. Cell Res (2023) 33:762-774. DOI 10.1038/s41422-023-00830-2 · PubMed

Other PDB entries of the same protein (UniProt Q14416 (AlphaFold model), which also has an AlphaFold model), best resolution first:

4XAQ 2.21 Å, mGluR2 ECD and mGluR3 ECD with ligands
4XAS 2.35 Å, mGluR2 ECD ligand complex
7EPE 2.5 Å, Crystal structure of mGlu2 bound to NAM563
5CNJ 2.65 Å, mGlur2 with glutamate analog
5CNI 2.69 Å, mGlu2 with Glutamate
7EPF 2.7 Å, Crystal structure of mGlu2 bound to NAM597
5KZN 2.8 Å, Metabotropic Glutamate Receptor
5KZQ 2.8 Å, Metabotropic Glutamate Receptor in complex with antagonist…
8JCU 2.8 Å, Cryo-EM structure of mGlu2-mGlu3 heterodimer in presence of LY341495 (dimerization mode I)
8JD2 2.8 Å, Cryo-EM structure of G protein-free mGlu2-mGlu3 heterodimer in Acc state
8JCY 2.9 Å, Cryo-EM structure of mGlu2-mGlu3 heterodimer in presence of LY341495, NAM563, and…
8JD4 2.9 Å, Cryo-EM structure of G protein-free mGlu2-mGlu4 heterodimer in Acc state

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