7RGP: PDB entry 7RGP

cryo-EM of human Glucagon-like peptide 1 receptor GLP-1R bound to tirzepatide. Determined by electron microscopy at 2.9 Å resolution. Released 13 Apr 2022.

Method: Electron microscopy
Resolution: 2.9 Å
Organisms: Homo sapiens, Mus musculus, Lama glama
Chains: 7
Atoms: 10,795
Mol. weight: 194.31 kDa
Released: 13 Apr 2022

Explore 7RGP in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7RGP contains 41 α-helices and 78 β-strands across 7 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, 6 β-strands

Element	Residues	Length	Sheet
α-helix	16-38	23
β-strand	40-45	6	1
α-helix	53-58	6
β-strand	209-214	6	1
β-strand	217-223	7	1
α-helix	235-237	3
β-strand	244-249	6	1
α-helix	265-278	14
β-strand	287-292	6	1
α-helix	295-302	8
α-helix	313-317	5
α-helix	326-327	2
α-helix	332-350	19
β-strand	359-361	3	1
α-helix	372-389	18

Chain B: 5 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	3-24	22
α-helix	34-36	3
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
β-strand	100-105	6	4
β-strand	111-116	6	4
β-strand	121-125	5	4
β-strand	134-139	6	4
β-strand	146-151	6	5
β-strand	156-161	6	5
β-strand	165-170	6	5
β-strand	175-181	7	5
α-helix	186	1
β-strand	187-191	5	6
β-strand	198-203	6	6
β-strand	207-212	6	6
β-strand	218-223	6	6
β-strand	229-234	6	7
β-strand	240-245	6	7
β-strand	249-254	6	7
β-strand	259-264	6	7
α-helix	272-273	2
β-strand	275-278	4	8
β-strand	284-288	5	8
β-strand	293-298	6	8
β-strand	303-309	7	8
β-strand	317-320	4	2
β-strand	327-330	4	2
β-strand	336-339	4	2

Chain E: 4 helices, 27 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	9
β-strand	10-12	3	10
β-strand	17-25	9	9
α-helix	29-31	3
β-strand	33-39	7	10
β-strand	45-51	7	10
β-strand	58-60	3	10
α-helix	62-64	3
β-strand	68-73	6	9
β-strand	78-84	7	9
β-strand	92-99	8	10
β-strand	110-111	2	10
β-strand	115-119	5	10
β-strand	129-130	2	11
β-strand	134-136	3	12
β-strand	143-148	6	11
β-strand	154	1	13
β-strand	160	1	13
β-strand	162	1	14
β-strand	164-167	4	12
β-strand	173-178	6	12
β-strand	182-183	2	12
α-helix	184	1
β-strand	193-196	4	11
β-strand	199-204	6	11
β-strand	214-215	2	12
β-strand	218	1	15
β-strand	219	1	14
α-helix	225	1
β-strand	227	1	15
β-strand	232-234	3	12

Chain G: 2 helices, 0 β-strands

Element	Residues	Length	Sheet
α-helix	8-23	16
α-helix	30-43	14

Chain N: 3 helices, 13 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	16
β-strand	11-12	2	17
β-strand	18-25	8	16
α-helix	29-31	3
β-strand	34-39	6	18
β-strand	45-50	6	18
β-strand	59-60	2	18
α-helix	62-64	3
β-strand	65	1	16
β-strand	68-73	6	16
β-strand	78-83	6	16
α-helix	88-90	3
β-strand	92-98	7	18
β-strand	118	1	18
β-strand	122-124	3	18
β-strand	125-126	2	17

Chain P: 1 helix, 0 β-strands

Element	Residues	Length	Sheet
α-helix	2-28	27

Chain R: 17 helices, 4 β-strands

Element	Residues	Length	Sheet
α-helix	32-51	20
α-helix	54-55	2
β-strand	83-84	2	19
α-helix	91-94	4
β-strand	99-100	2	19
β-strand	104	1	20
β-strand	110	1	20
α-helix	119-120	2
α-helix	140-159	20
α-helix	162-165	4
α-helix	175-205	31
α-helix	224-242	19
α-helix	245-256	12
α-helix	262-291	30
α-helix	304-335	32
α-helix	349-355	7
α-helix	357-360	4
α-helix	362-367	6
α-helix	378-392	15
α-helix	394-402	9
α-helix	407-420	14

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(i) subunit alpha-3,Isoform Gnas-2 of Guanine…	A	protein	373	Homo sapiens	P08754 (AlphaFold model), P63092 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	350	Homo sapiens	P62873 (AlphaFold model)
Single-chain variable fragment 16	E	protein	297	Mus musculus
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	71	Homo sapiens	P59768 (AlphaFold model)
nanobody 35	N	protein	160	Lama glama
Tirzepatide	P	protein	39	Homo sapiens
Glucagon-like peptide 1 receptor	R	protein	445	Homo sapiens	P43220

Sequence of entity 1 (A), FASTA

>7RGP_1 Guanine nucleotide-binding protein G(i) subunit alpha-3,Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains A)
MGCTLSAEDKAAVERSKMIEKQLQKDKQVYRATHRLLLLGAGESGKSTIVKQMRILHVNG
FNGDSEKATKVQDIKNNLKEAIETIVAAMSNLVPPVELANPENQFRVDYILSVMNVPDFD
FPPEFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLDKIDVIKQADYVPSDQDLLRCR
VLTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTAIIFVVASSSYNMVIREDN
QTNRLQEALNLFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTP
EDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCAVDTENIRRVFNDCRD
IIQRMHLRQYELL

Sequence of entity 2 (B), FASTA

>7RGP_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MHHHHHHGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRT
LRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGN
YVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWD
IETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDIN
AICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYD
DFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (E), FASTA

>7RGP_3 Single-chain variable fragment 16 (chains E)
MLLVNQSHQGFNKEHTSKMVSAIVLYVLLAAAAHSAFADVQLVESGGGLVQPGGSRKLSC
SASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYYADTVKGRFTISRDDPKNTLFLQ
MTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVSSGGGGSGGGGSGGGGSDIVMTQ
ATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQRPGQSPQLLIYRMSNLASGVPDR
FSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFGAGTKLELKAAAHHHHHHHH

Sequence of entity 4 (G), FASTA

>7RGP_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 5 (N), FASTA

>7RGP_5 nanobody 35 (chains N)
MKYLLPTAAAGLLLLAAQPAMAQVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVR
QAPGKGLEWVSDISQSGASISYTGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCAR
CPAPFTRDCFDVTSTTYAYRGQGTQVTVSSHHHHHHEPEA

Sequence of entity 6 (P), FASTA

>7RGP_6 Tirzepatide (chains P)
YAEGTFTSDYSIALDKIAQKAFVQWLIAGGPSSGAPPPS

Sequence of entity 7 (R), FASTA

>7RGP_7 Glucagon-like peptide 1 receptor (chains R)
MKTIIALSYIFCLVFADYKDDDDAAAGGSGGSLEVLFQGPGGSGGSRPQGATVSLWETVQ
KWREYRRQCQRSLTEDPPPATDLFCNRTFDEYACWPDGEPGSFVNVSCPWYLPWASSVPQ
GHVYRFCTAEGLWLQKDNSSLPWRDLSECEESKRGERSSPEEQLLFLYIIYTVGYALSFS
ALVIASAILLGFRHLHCTRNYIHLNLFASFILRALSVFIKDAALKWMYSTAAQQHQWDGL
LSYQDSLSCRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVFSEQWIFRLYVSIGWGVP
LLFVVPWGIVKYLYEDEGCWTRNSNMNYWLIIRLPILFAIGVNFLIFVRVICIVVSKLKA
NLMCKTDIKCRLAKSTLTLIPLLGTHEVIFAFVMDEHARGTLRFIKLFTELSFTSFQGLM
VAILYCFVNNEVQLEFRKSWERWRL

Primary citation

Structural determinants of dual incretin receptor agonism by tirzepatide. Sun, B., Willard, F.S., Feng, D. et al. Proc Natl Acad Sci U S A (2022) 119:e2116506119-e2116506119. DOI 10.1073/pnas.2116506119 · PubMed

Other PDB entries of the same protein (UniProt P08754 (AlphaFold model), which also has an AlphaFold model), best resolution first:

2ODE 1.9 Å, Crystal structure of the heterodimeric complex of human RGS8 and activated Gi alpha 3
9YCX 2.1 Å, Neurotensin Receptor 1 (NTSR1) bound to Octotensin in complex with Gi3 in the…
9YCY 2.2 Å, Neurotensin Receptor 1 (NTSR1) bound to Octotensin in complex with Gi3 in the Canonical…
8IKL 2.33 Å, Cryo-EM structure of the CD97-G13 complex
8YK0 2.4 Å, Cryo-EM structure of human GPR156-Gi3 complex
7T10 2.5 Å, CryoEM structure of somatostatin receptor 2 in complex with somatostatin-14 and Gi3
9VJ6 2.62 Å, Cryo-EM structure of 5-HT1AR-Gi3 in complex with F-15599
7T11 2.7 Å, CryoEM structure of somatostatin receptor 2 in complex with Octreotide and Gi3.
9VJF 2.7 Å, Cryo-EM structure of 5-HT1AR-Gi3 in complex with buspirone
2IHB 2.71 Å, Crystal structure of the heterodimeric complex of human RGS10 and activated Gi alpha 3
2V4Z 2.8 Å, The crystal structure of the human G-protein subunit alpha (GNAI3) in complex with an…
7KH0 2.8 Å, Cryo-EM structure of the human arginine vasopressin AVP-vasopressin receptor V2R-Gs…

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