7TRS: PDB entry 7TRS

Human M4 muscarinic acetylcholine receptor complex with Gi1 and the endogenous agonist acetylcholine. Determined by electron microscopy at 2.8 Å resolution. Released 17 May 2023.

Method: Electron microscopy
Resolution: 2.8 Å
Organisms: Homo sapiens, Mus musculus
Chains: 5
Atoms: 8,571
Mol. weight: 152.76 kDa
Ligands: ACH
Released: 17 May 2023

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

Secondary structure: helices and β-sheets

7TRS contains 38 α-helices and 62 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 A: 8 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	7-31	25
β-strand	34-40	7	14
β-strand	185-190	6	14
β-strand	195-200	6	14
α-helix	208-210	3
α-helix	212-215	4
β-strand	220-226	7	14
β-strand	233	1	15
β-strand	241	1	15
α-helix	242-254	13
β-strand	263-269	7	14
α-helix	271-280	10
α-helix	283-285	3
α-helix	296-308	13
β-strand	319-323	5	14
α-helix	330-351	22

Chain B: 5 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	4-24	21
α-helix	30-33	4
α-helix	38-39	2
β-strand	47-52	6	1
β-strand	58-63	6	2
β-strand	69-74	6	2
β-strand	78-83	6	2
β-strand	88-94	7	2
α-helix	95	1
β-strand	100-105	6	3
β-strand	111-116	6	3
β-strand	120-125	6	3
β-strand	134-140	7	3
β-strand	146-151	6	4
β-strand	156-161	6	4
β-strand	165-170	6	4
β-strand	176-181	6	4
α-helix	186	1
β-strand	187-192	6	5
β-strand	198-203	6	5
β-strand	207-212	6	5
β-strand	218-223	6	5
β-strand	229-234	6	6
β-strand	240-245	6	6
β-strand	250-254	5	6
β-strand	260-264	5	6
β-strand	273-278	6	7
β-strand	284-289	6	7
β-strand	294-298	5	7
β-strand	303-307	5	7
β-strand	317-320	4	1
β-strand	327-330	4	1
β-strand	335-339	5	1

Chain G: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	9-23	15
α-helix	30-43	14
α-helix	54-55	2

Chain H: 4 helices, 26 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	8
β-strand	11-12	2	9
β-strand	17-25	9	8
α-helix	29-31	3
β-strand	34-39	6	10
β-strand	45-51	7	10
α-helix	53-55	3
β-strand	58-60	3	10
β-strand	65	1	8
β-strand	68-73	6	8
β-strand	78-84	7	8
α-helix	88-90	3
β-strand	93-98	6	10
β-strand	110-111	2	10
β-strand	115-116	2	10
β-strand	118-119	2	9
β-strand	141	1	11
β-strand	146-148	3	12
β-strand	155-160	6	11
β-strand	166	1	13
β-strand	172	1	13
β-strand	174-179	6	12
β-strand	185-190	6	12
β-strand	194-195	2	12
β-strand	203-207	5	11
β-strand	211-216	6	11
β-strand	225-231	7	12
α-helix	237	1
β-strand	239	1	12
β-strand	243-246	4	12

Chain R: 18 helices, 0 β-strands

Element	Residues	Length
α-helix	34-59	26
α-helix	61-63	3
α-helix	66-80	15
α-helix	81-85	5
α-helix	86-95	10
α-helix	102-135	34
α-helix	140-143	4
α-helix	146-175	30
α-helix	188-190	3
α-helix	193-200	8
α-helix	201-205	5
α-helix	206-220	15
α-helix	393-423	31
α-helix	427-429	3
α-helix	432-447	16
α-helix	449	1
α-helix	450-454	5
α-helix	458-465	8

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	349	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	70	Homo sapiens	P59768 (AlphaFold model)
Antibody fragment scFv16	H	protein	248	Mus musculus
Guanine nucleotide-binding protein G(i) subunit alpha-1	A	protein	354	Homo sapiens	P63096 (AlphaFold model)
Muscarinic acetylcholine receptor M4	R	protein	349	Homo sapiens	P08173 (AlphaFold model)

Sequence of entity 1 (B), FASTA

>7TRS_1 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
HHHHHHGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTL
RGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNY
VACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDI
ETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINA
ICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDD
FNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 2 (G), FASTA

>7TRS_2 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
ASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENPF
REKKFFCAIL

Sequence of entity 3 (H), FASTA

>7TRS_3 Antibody fragment scFv16 (chains H)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELK

Sequence of entity 4 (A), FASTA

>7TRS_4 Guanine nucleotide-binding protein G(i) subunit alpha-1 (chains A)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKNTIVKQMKIIHEAG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TTGIVETHFTFKDLHFKMFDVGAQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEM
NRMHASMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAA
AYIQCQFEDLNKRKDTKEIYTHFTCSTDTKNVQFVFDAVTDVIIKNNLKDCGLF

Sequence of entity 5 (R), FASTA

>7TRS_5 Muscarinic acetylcholine receptor M4 (chains R)
DYKDDDDAMANFTPVNGSSGNQSVRLVTSSSHNRYETVEMVFIATVTGSLSLVTVVGNIL
VMLSIKVNRQLQTVNNYFLFSLACADLIIGAFSMNLYTVYIIKGYWPLGAVVCDLWLALD
YVVSNASVMNLLIISFDRYFCVTKPLTYPARRTTKMAGLMIAAAWVLSFVLWAPAILFWQ
FVVGKRTVPDNQCFIQFLSNPAVTFGTAIAAFYLPVVIMTVLYIHISLASRSRVHKHRPE
GPKEKKAKTKRQMAARERKVTRTIFAILLAFILTWTPYNVMVLVNTFCQSCIPDTVWSIG
YWLCYVNSTINPACYALCNATFKKTFRHLLLCQYRNIGTARHHHHHHHH

Ligands and cofactors

ID	Name	Formula	Copies
ACH	Acetylcholine	C7 H16 N O2	1

Primary citation

Structural and dynamic mechanisms of allostery at the M4 muscarinic acetylcholine receptor. Thal, D.M. Elife (2023).

Other PDB entries of the same protein (UniProt P62873 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8QEH 1.43 Å, Crystal structure of the G11 protein heterotrimer bound to FR900359 inhibitor
8QEG 1.7 Å, Crystal structure of the G11 protein heterotrimer bound to YM-254890 inhibitor
8F0K 1.9 Å, Human Amylin3 Receptor in complex with Gs and Pramlintide analogue peptide San385
9YDQ 1.94 Å, Human delta opioid receptor complex with mini-Gi and agonist DADLE and allosteric…
9YDP 1.95 Å, Human delta opioid receptor complex with mini-Gi and agonist DADLE
6CRK 2.0 Å, Heterotrimeric G-protein in complex with an antibody fragment
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

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