8JIU: PDB entry 8JIU
Cryo-EM structure of the GLP-1R/GCGR dual agonist SAR425899-bound human GCGR-Gs complex. Determined by electron microscopy at 2.76 Å resolution. Released 13 Sept 2023.
- Method
- Electron microscopy
- Resolution
- 2.76 Å
- Organisms
- Homo sapiens, synthetic construct, Rattus norvegicus
- Chains
- 6
- Atoms
- 9,075
- Mol. weight
- 156.93 kDa
- Ligands
- D6M
- Released
- 13 Sept 2023
Explore 8JIU in 3D
Show helices and sheets
RCSB PDB
PDBe
Secondary structure: helices and β-sheets
8JIU contains 42 α-helices and 54 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: 10 helices, 6 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 10-37 | 28 | |
| β-strand | 40-47 | 8 | 1 |
| α-helix | 53-55 | 3 | |
| β-strand | 209-214 | 6 | 1 |
| β-strand | 217-223 | 7 | 1 |
| α-helix | 234-237 | 4 | |
| β-strand | 243-249 | 7 | 1 |
| α-helix | 265-277 | 13 | |
| β-strand | 286-292 | 7 | 1 |
| α-helix | 295-297 | 3 | |
| α-helix | 299-302 | 4 | |
| α-helix | 308-311 | 4 | |
| α-helix | 325-327 | 3 | |
| α-helix | 332-351 | 20 | |
| β-strand | 359-363 | 5 | 1 |
| α-helix | 371-390 | 20 | |
Chain B: 4 helices, 28 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 4-24 | 21 | |
| α-helix | 31-35 | 5 | |
| α-helix | 38-39 | 2 | |
| β-strand | 47-50 | 4 | 2 |
| β-strand | 58-63 | 6 | 3 |
| β-strand | 70-74 | 5 | 3 |
| β-strand | 78-81 | 4 | 3 |
| β-strand | 91-94 | 4 | 3 |
| β-strand | 100-105 | 6 | 4 |
| β-strand | 111-116 | 6 | 4 |
| β-strand | 121-125 | 5 | 4 |
| β-strand | 135-139 | 5 | 4 |
| α-helix | 145 | 1 | |
| β-strand | 146-151 | 6 | 5 |
| β-strand | 156-161 | 6 | 5 |
| β-strand | 166-170 | 5 | 5 |
| β-strand | 176-180 | 5 | 5 |
| β-strand | 187-192 | 6 | 6 |
| β-strand | 198-203 | 6 | 6 |
| β-strand | 207-212 | 6 | 6 |
| β-strand | 217-223 | 7 | 6 |
| β-strand | 229-234 | 6 | 7 |
| β-strand | 240-245 | 6 | 7 |
| β-strand | 250-254 | 5 | 7 |
| β-strand | 259-263 | 5 | 7 |
| β-strand | 273-278 | 6 | 8 |
| β-strand | 284-289 | 6 | 8 |
| β-strand | 294-298 | 5 | 8 |
| β-strand | 304-308 | 5 | 8 |
| β-strand | 315-320 | 6 | 2 |
| β-strand | 327-331 | 5 | 2 |
| β-strand | 336-339 | 4 | 2 |
Chain C: 4 helices, 0 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 8-21 | 14 | |
| α-helix | 43-45 | 3 | |
| α-helix | 54-55 | 2 | |
| α-helix | 56-58 | 3 | |
Chain N: 3 helices, 14 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 | 34-39 | 6 | 11 |
| β-strand | 41 | 1 | 12 |
| β-strand | 43 | 1 | 12 |
| β-strand | 45-51 | 7 | 11 |
| β-strand | 58-60 | 3 | 11 |
| α-helix | 62-64 | 3 | |
| β-strand | 69-73 | 5 | 9 |
| β-strand | 78-82 | 5 | 9 |
| α-helix | 88-90 | 3 | |
| β-strand | 92-98 | 7 | 11 |
| β-strand | 118 | 1 | 11 |
| β-strand | 122-124 | 3 | 11 |
| β-strand | 125-126 | 2 | 10 |
Chain P: 1 helix, 0 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 3-28 | 26 | |
Chain R: 20 helices, 6 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 30-46 | 17 | |
| β-strand | 63 | 1 | 13 |
| β-strand | 66 | 1 | 13 |
| α-helix | 79 | 1 | |
| β-strand | 80 | 1 | 14 |
| α-helix | 81-82 | 2 | |
| α-helix | 86-90 | 5 | |
| β-strand | 95 | 1 | 14 |
| α-helix | 106-107 | 2 | |
| β-strand | 108 | 1 | 15 |
| β-strand | 114 | 1 | 15 |
| α-helix | 125-163 | 39 | |
| α-helix | 172-200 | 29 | |
| α-helix | 209-215 | 7 | |
| α-helix | 221-251 | 31 | |
| α-helix | 264-268 | 5 | |
| α-helix | 269-273 | 5 | |
| α-helix | 274-288 | 15 | |
| α-helix | 301-303 | 3 | |
| α-helix | 305-307 | 3 | |
| α-helix | 309-335 | 27 | |
| α-helix | 344-352 | 9 | |
| α-helix | 355-357 | 3 | |
| α-helix | 361-364 | 4 | |
| α-helix | 375-401 | 27 | |
| α-helix | 405-416 | 12 | |
Molecules and chains
| Molecule | Chains | Type | Length | Organism | UniProt |
|---|
| Guanine nucleotide-binding protein G(s) subunit alpha isoforms short | A | protein | 394 | Homo sapiens | P63092 (AlphaFold model) |
| SAR425899 | P | protein | 29 | synthetic construct | |
| Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 | B | protein | 345 | Rattus norvegicus | P54311 (AlphaFold model) |
| Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 | C | protein | 70 | Bos taurus | P63212 (AlphaFold model) |
| Nanobody 35 | N | protein | 140 | Escherichia coli | |
| Glucagon receptor | R | protein | 405 | Homo sapiens | P47871 (AlphaFold model) |
Sequence of entity 1 (A), FASTA
>8JIU_1 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains A)
MGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGAGESGKNTIVKQM
RILHVNGFNGEGGEEDPQAARSNSDGEKATKVQDIKNNLKEAIETIVAAMSNLVPPVELA
NPENQFRVDYILSVMNVPDFDFPPEFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLD
KIDVIKQADYVPSDQDLLRCRVLTSGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFND
VTAIIFVVASSSYNMVIREDNQTNRLQAALKLFDSIWNNKWLRDTSVILFLNKQDLLAEK
VLAGKSKIEDYFPEFARYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCY
PHFTCAVDTENIRRVFNDCRDIIQRMHLRQYELL
Sequence of entity 2 (P), FASTA
>8JIU_2 SAR425899 (chains P)
HSQGTFTSDLSKQKESKAAQDFIEWLKAG
Sequence of entity 3 (B), FASTA
>8JIU_3 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MGSLLQSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHL
AKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACG
GLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQ
QTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFF
PNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCN
VWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN
Sequence of entity 4 (C), FASTA
>8JIU_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains C)
ASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENPF
REKKFFCAIL
Sequence of entity 5 (N), FASTA
>8JIU_5 Nanobody 35 (chains N)
MAQVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASI
SYTGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYR
GQGTQVTVSSHHHHHHEPEA
Sequence of entity 6 (R), FASTA
>8JIU_6 Glucagon receptor (chains R)
QVMDFLFEKWKLYGDQCHHNLSLLPPPTELVCNRTFDKYSCWPDTPANTTANISCPWYLP
WHHKVQHRFVFKRCGPDGQWVRGPRGQPWRDASQCQMDGEEIEVQKEVAKMYSSFQVMYT
VGYSLSLGALLLALAILGGLSKLHCTRNAIHANLFASFVLKASSVLVIDGLLRTRYSQKI
GDDLSVSTWLSDGAVAGCRVAAVFMQYGIVANYCWLLVEGLYLHNLLGLATLPERSFFSL
YLGIGWGAPMLFVVPWAVVKCLFENVQCWTSNDNMGFWWILRFPVFLAILINFFIFVRIV
QLLVAKLRARQMHHTDYKFRLAKSTLTLIPLLGVHEVVFAFVTDEHAQGTLRSAKLFFDL
FLSSFQGLLVAVLYCFLNKEVQSELRRRWHRWRLGKVLWEERNTS
Ligands and cofactors
| ID | Name | Formula | Copies |
|---|
| D6M | N-hexadecanoyl-L-glutamic acid | C21 H39 N O5 | 1 |
Primary citation
Structural analysis of the dual agonism at GLP-1R and GCGR. Li, Y., Zhou, Q., Dai, A. et al. Proc Natl Acad Sci U S A (2023) 120:e2303696120-e2303696120. DOI 10.1073/pnas.2303696120 · PubMed
Other PDB entries of the same protein (UniProt P63092 (AlphaFold model), which also has an AlphaFold model), best resolution first:
- 7BPH 1.57 Å, Crystal structure of GppNHp-bound GNAS in complex with the cyclic peptide inhibitor GN13
- 6AU6 1.7 Å, Crystal structure of GDP-bound human GNAS R201C mutant
- 8F0K 1.9 Å, Human Amylin3 Receptor in complex with Gs and Pramlintide analogue peptide San385
- 7E5E 1.95 Å, Crystal structure of GDP-bound GNAS in complex with the cyclic peptide inhibitor GD20
- 7MBX 1.95 Å, Human Cholecystokinin 1 receptor (CCK1R) Gs complex
- 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
- 7RTB 2.14 Å, Peptide-19 bound to the Glucagon-Like Peptide-1 Receptor (GLP-1R)
Browse structure collections
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