8JRV: Glucagon receptor

Cryo-EM structure of the glucagon receptor bound to glucagon and beta-arrestin 1. Determined by electron microscopy at 3.3 Å resolution. Released 16 Aug 2023.

Method: Electron microscopy
Resolution: 3.3 Å
Organisms: Influenza A virus (strain A/Victoria/3/1975 H3N2), Homo sapiens, Escherichia phage EcSzw-2
Chains: 6
Atoms: 7,707
Mol. weight: 279.79 kDa
Ligands: PIO
Released: 16 Aug 2023

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

Secondary structure: helices and β-sheets

8JRV contains 30 α-helices and 72 β-strands across 6 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, 31 β-strands

Element	Residues	Length	Sheet
β-strand	7-12	6	1
β-strand	18-22	5	1
β-strand	26-28	3	2
β-strand	29	1	3
β-strand	34	1	3
α-helix	35-36	2
β-strand	37-43	7	1
β-strand	53-56	4	4
β-strand	59-62	4	4
β-strand	76-80	5	4
β-strand	83-85	3	4
α-helix	95-98	4
α-helix	99-108	10
β-strand	113-117	5	1
α-helix	119-120	2
β-strand	127-129	3	5
β-strand	142-150	9	4
β-strand	164-168	5	4
β-strand	169-171	3	2
α-helix	180-182	3
β-strand	183-188	6	6
α-helix	195-196	2
β-strand	197-203	7	6
β-strand	207-208	2	7
β-strand	214-222	9	6
β-strand	228-239	12	8
β-strand	242	1	9
β-strand	246	1	9
β-strand	252-258	7	8
β-strand	262	1	8
β-strand	266-274	9	6
β-strand	288-290	3	5
β-strand	300	1	5
α-helix	301-303	3
β-strand	319-329	11	8
β-strand	342-349	8	8
β-strand	350-351	2	7
α-helix	353-355	3
α-helix	359-361	3
β-strand	367	1	10

Chain B: 3 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	4-7	4	19
β-strand	11-12	2	20
β-strand	19-24	6	19
α-helix	33	1
β-strand	34-38	5	21
β-strand	46-51	6	21
β-strand	58-59	2	21
α-helix	61-63	3
β-strand	69-72	4	19
α-helix	74-76	3
β-strand	77-81	5	19
β-strand	91-97	7	21
β-strand	108-110	3	21
β-strand	111-112	2	20

Chain G: 1 helix, 0 β-strands

Element	Residues	Length	Sheet
α-helix	2-24	23

Chain H: 1 helix, 12 β-strands

Element	Residues	Length	Sheet
β-strand	8-10	3	11
β-strand	14	1	12
β-strand	20-26	7	11
β-strand	35-42	8	13
β-strand	48-55	8	13
β-strand	60-63	4	13
β-strand	72-76	5	11
β-strand	81-87	7	11
α-helix	91-93	3
β-strand	95-103	9	13
β-strand	112	1	13
β-strand	117-119	3	13
β-strand	120	1	12

Chain L: 1 helix, 17 β-strands

Element	Residues	Length	Sheet
β-strand	5-6	2	14
β-strand	11-13	3	15
β-strand	20-21	2	16
β-strand	24	1	16
β-strand	25-26	2	14
β-strand	34	1	17
β-strand	35-39	5	15
β-strand	46-50	5	15
β-strand	54-55	2	15
β-strand	63-68	6	16
β-strand	71-76	6	16
α-helix	81-83	3
β-strand	86-88	3	15
β-strand	90	1	18
β-strand	91	1	17
β-strand	94	1	10
β-strand	99	1	18
β-strand	103-106	4	15

Chain R: 15 helices, 1 β-strand

Element	Residues	Length	Sheet
α-helix	28-46	19
α-helix	128-165	38
α-helix	167-170	4
α-helix	172-206	35
α-helix	224-253	30
α-helix	264-271	8
α-helix	274-277	4
α-helix	280-287	8
α-helix	305-336	32
α-helix	343-366	24
α-helix	380-390	11
α-helix	392-397	6
α-helix	398-402	5
α-helix	405-424	20
α-helix	1357-1359	3
β-strand	1360-1364	5	1

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
HA signal peptide,HPC4 purification tag,Glucagon receptor,C-terminal tail of Vasopressin V2 receptor	R	protein	476	Influenza A virus (strain A/Victoria/3/1975 H3N2), Homo sapiens	P03435, P04070 (AlphaFold model), P30518 (AlphaFold model), P47871 (AlphaFold model)
Glucagon	G	protein	29	Homo sapiens	P01275
Beta-arrestin 1 and single-chain fragment variable 30 (scFv30)	A, H, L	protein	627	Homo sapiens	P49407
Nanobody 32	B	protein	126	Escherichia phage EcSzw-2

Sequence of entity 1 (R), FASTA

>8JRV_1 HA signal peptide,HPC4 purification tag,Glucagon receptor,C-terminal tail of Vasopressin V2 receptor (chains R)
MKTIIALSYIFCLVFAGAPEDQVDPRLIDGKGSGSAGSAGSQVMDFLFEKWKLYGDQCHH
NLSLLPPPTELVCNRTFDKYSCWPDTPANTTANISCPWYLPWHHKVQHRFVFKRCGPDGQ
WVRGPRGQPWRDASQCQMDGEEIEVQKEVAKMYSSFQVMYTVGYSLSLGALLLALAILGG
LSKLHCTRNAIHANLFASFVLKASSVLVIDGLLRTRYSQKIGDDLSVSTWLSDGAVAGCR
VAAVFMQYGIVANYCWLLVEGLYLHNLLGLATLPERSFFSLYLGIGWGAPMLFVVPWAVV
KCLFENVQCWTSNDNMGFWWILRFPVFLAILINFFIFVRIVQLLVAKLRARQMHHTDYKF
RLAKSTLTLIPLLGVHEVVFAFVTDEHAQGTLRSAKLFFDLFLSSFQGLLVAVLYCFLNK
EVQSELRRRWHRWRLGKVLWEERNTSNARGRTPPSLGPQDESCTTASSSLAKDTSS

Sequence of entity 2 (G), FASTA

>8JRV_2 Glucagon (chains G)
HSQGTFTSDYSKYLDSRRAQDFVQWLMNT

Sequence of entity 3 (A, H, L), FASTA

>8JRV_3 Beta-arrestin 1 and single-chain fragment variable 30 (scFv30) (chains A, H, L)
MGDKGTRVFKKASPNGKLTVYLGKRDFVDHIDLVEPVDGVVLVDPEYLKERRVYVTLTAA
FRYGREDLDVLGLTFRKDLFVANVQSFPPAPEDKKPLTRLQERLIKKLGEHAYPFTFEIP
PNLPSSVTLQPGPEDTGKAIGVDYEVKAFVAENLEEKIHKRNSVRLVIEKVQYAPERPGP
QPTAETTRQFLMSDKPLHLEASLDKEIYYHGEPISVNVHVTNNTNKTVKKIKISVRQYAD
IVLFNTAQYKVPVAMEEADDTVAPSSTFSKVYTLTPFLANNREKRGLALDGKLKHEDTNL
ASSTLLREGANREILGIIVSYKVKVKLVVSRGGLLGDLASSDVAVELPFTLMHPKPKEEP
PHREVPEHETPVDTNLSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKA
PKLLIYSASSLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQYKYVPVTFGQGTK
VEIKGTTAASGSSGGSSSGAEVQLVESGGGLVQPGGSLRLSCAASGFNVYSSSIHWVRQA
PGKGLEWVASISSYYGYTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSR
QFWYSGLDYWGQGTLVTVSSAHHHHHH

Sequence of entity 4 (B), FASTA

>8JRV_4 Nanobody 32 (chains B)
MAQVQLQESGGGLVQAGGSLRLSCVVSGFFFDTVTMAWYRRAPGKHRELVASATAGGTTT
YADSVKDRFTISRDNAKNTVYLQMNSLKPEDTAVYYCNTFVRSLSWGQGTQVTVSSHHHH
HHEPEA

Ligands and cofactors

ID	Name	Formula	Copies
PIO	[(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-d…	C25 H49 O19 P3	1

Primary citation

Tail engagement of arrestin at the glucagon receptor. Chen, K., Zhang, C., Lin, S. et al. Nature (2023) 620:904-910. DOI 10.1038/s41586-023-06420-x · PubMed

Other PDB entries of the same protein (UniProt P03435), best resolution first:

6R0E 1.91 Å, Structure of F11TCR in complex with DR1 MHC Class II presenting PKYVKQNTLKLAT
8IOD 2.59 Å, Cryo-EM structure of the PG-901-bound human melanocortin receptor 5 (MC5R)-Gs complex
8INR 2.73 Å, Cryo-EM structure of the alpha-MSH-bound human melanocortin receptor 5 (MC5R)-Gs complex
4O58 2.75 Å, Crystal structure of broadly neutralizing antibody F045-092 in complex with…
8IOC 2.86 Å, Cryo-EM structure of the gamma-MSH-bound human melanocortin receptor 3 (MC3R)-Gs complex
4GMS 2.95 Å, Crystal structure of heterosubtypic Fab S139/1 in complex with influenza A H3…
8JRU 3.5 Å, Cryo-EM structure of the glucagon receptor bound to beta-arrestin 1 in ligand-free state

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