8JIR: PDB entry 8JIR
Cryo-EM structure of the GLP-1R/GCGR dual agonist SAR425899-bound human GLP-1R-Gs complex. Determined by electron microscopy at 2.57 Å resolution. Released 6 Sept 2023.
- Method
- Electron microscopy
- Resolution
- 2.57 Å
- Organisms
- Homo sapiens, synthetic construct, Rattus norvegicus
- Chains
- 6
- Atoms
- 9,014
- Mol. weight
- 157.37 kDa
- Ligands
- D6M
- Released
- 6 Sept 2023
Explore 8JIR in 3D
Show helices and sheets
RCSB PDB
PDBe
Secondary structure: helices and β-sheets
8JIR contains 33 α-helices and 48 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: 7 helices, 6 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 8-30 | 23 | |
| β-strand | 33-40 | 8 | 1 |
| β-strand | 184-191 | 8 | 1 |
| β-strand | 194-201 | 8 | 1 |
| α-helix | 212-215 | 4 | |
| β-strand | 220-226 | 7 | 1 |
| α-helix | 233-245 | 13 | |
| β-strand | 253-259 | 7 | 1 |
| α-helix | 261-270 | 10 | |
| α-helix | 280-283 | 4 | |
| α-helix | 301-318 | 18 | |
| β-strand | 326-329 | 4 | 1 |
| α-helix | 339-357 | 19 | |
Chain B: 4 helices, 28 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 2-22 | 21 | |
| α-helix | 30-33 | 4 | |
| α-helix | 38-39 | 2 | |
| β-strand | 47-51 | 5 | 2 |
| β-strand | 58-63 | 6 | 3 |
| β-strand | 69-74 | 6 | 3 |
| β-strand | 78-83 | 6 | 3 |
| β-strand | 89-94 | 6 | 3 |
| α-helix | 95 | 1 | |
| β-strand | 100-105 | 6 | 4 |
| β-strand | 111-116 | 6 | 4 |
| β-strand | 121-125 | 5 | 4 |
| β-strand | 134-138 | 5 | 4 |
| β-strand | 146-153 | 8 | 5 |
| β-strand | 156-161 | 6 | 5 |
| β-strand | 165-170 | 6 | 5 |
| β-strand | 175-181 | 7 | 5 |
| β-strand | 187-192 | 6 | 6 |
| β-strand | 198-203 | 6 | 6 |
| β-strand | 207-212 | 6 | 6 |
| β-strand | 221-222 | 2 | 6 |
| β-strand | 229-234 | 6 | 7 |
| β-strand | 240-245 | 6 | 7 |
| β-strand | 250-254 | 5 | 7 |
| β-strand | 259-264 | 6 | 7 |
| β-strand | 276-278 | 3 | 8 |
| β-strand | 284-288 | 5 | 8 |
| β-strand | 294-298 | 5 | 8 |
| β-strand | 304-307 | 4 | 8 |
| β-strand | 315-320 | 6 | 2 |
| β-strand | 327-331 | 5 | 2 |
| β-strand | 336-339 | 4 | 2 |
Chain G: 3 helices, 0 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 8-23 | 16 | |
| α-helix | 30-44 | 15 | |
| α-helix | 53-55 | 3 | |
Chain N: 1 helix, 12 β-strands
| Element | Residues | Length | Sheet |
|---|
| β-strand | 3-7 | 5 | 9 |
| β-strand | 11-12 | 2 | 10 |
| β-strand | 18-25 | 8 | 9 |
| β-strand | 34-39 | 6 | 11 |
| β-strand | 45-51 | 7 | 11 |
| β-strand | 59-60 | 2 | 11 |
| α-helix | 62-64 | 3 | |
| β-strand | 68-73 | 6 | 9 |
| β-strand | 78-83 | 6 | 9 |
| 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 | 3-23 | 21 | |
Chain R: 17 helices, 2 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 32-52 | 21 | |
| β-strand | 80-82 | 3 | 12 |
| α-helix | 84-86 | 3 | |
| α-helix | 90-93 | 4 | |
| β-strand | 101-103 | 3 | 12 |
| α-helix | 139-168 | 30 | |
| α-helix | 175-199 | 25 | |
| α-helix | 208-214 | 7 | |
| α-helix | 224-256 | 33 | |
| α-helix | 258-259 | 2 | |
| α-helix | 264-275 | 12 | |
| α-helix | 278-291 | 14 | |
| α-helix | 304-309 | 6 | |
| α-helix | 311-337 | 27 | |
| α-helix | 345-360 | 16 | |
| α-helix | 362-365 | 4 | |
| α-helix | 378-399 | 22 | |
| α-helix | 400-404 | 5 | |
| α-helix | 407-418 | 12 | |
Molecules and chains
| Molecule | Chains | Type | Length | Organism | UniProt |
|---|
| Guanine nucleotide-binding protein G(s) subunit alpha isoforms short | A | protein | 361 | Homo sapiens | P63092 (AlphaFold model), P63096 (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 | G | protein | 70 | Bos taurus | P63212 (AlphaFold model) |
| Nanobody 35 | N | protein | 140 | Escherichia coli | |
| Glucagon-like peptide 1 receptor | R | protein | 440 | Homo sapiens | P43220 |
Sequence of entity 1 (A), FASTA
>8JIR_1 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains A)
MGCTLSAEDKAAVERSKMIEKQLQKDKQVYRATHRLLLLGADNSGKSTIVKQMRIYHVNG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TSGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFNDVTAIIFVVDSSDYNRLQEALNDF
KSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEPGEDPR
VTRAKYFIRDEFLRISTASGDGRHYCYPHFTCAVDTENIRRVFNDCRDIIQRMHLRQYEL
L
Sequence of entity 2 (P), FASTA
>8JIR_2 SAR425899 (chains P)
HSQGTFTSDLSKQKESKAAQDFIEWLKAG
Sequence of entity 3 (B), FASTA
>8JIR_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 (G), FASTA
>8JIR_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
ASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENPF
REKKFFCAIL
Sequence of entity 5 (N), FASTA
>8JIR_5 Nanobody 35 (chains N)
MAQVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASI
SYTGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYR
GQGTQVTVSSHHHHHHEPEA
Sequence of entity 6 (R), FASTA
>8JIR_6 Glucagon-like peptide 1 receptor (chains R)
RPQGATVSLWETVQKWREYRRQCQRSLTEDPPPATDLFCNRTFDEYACWPDGEPGSFVNV
SCPWYLPWASSVPQGHVYRFCTAEGLWLQKDNSSLPWRDLSECEESKRGERSSPEEQLLF
LYIIYTVGYALSFSALVIASAILLGFRHLHCTRNYIHLNLFASFILRALSVFIKDAALKW
MYSTAAQQHQWDGLLSYQDSLSCRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVLSEQ
WIFRLYVSIGWGVPLLFVVPWGIVKYLYEDEGCWTRNSNMNYWLIIRLPILFAIGVNFLI
FVRVICIVVSKLKANLMCKTDIKCRLAKSTLTLIPLLGTHEVIFAFVMDEHARGTLRFIK
LFTELSFTSFQGLMVAILYCFVNNEVQLEFRKSWERWRLEHLHIQRDSSMKPLKCPTSSL
SSGATAGSSMYTATCQASCS
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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