7T96: Muscarinic acetylcholine receptor M2

Cryo-EM structure of S2 state ACh-bound M2R-Go signaling complex with a PAM. Determined by electron microscopy at 3.22 Å resolution. Released 25 Jan 2023.

Method: Electron microscopy
Resolution: 3.22 Å
Organisms: Homo sapiens, Mus musculus
Chains: 5
Atoms: 8,450
Mol. weight: 153.35 kDa
Ligands: 2CU, ACH
Released: 25 Jan 2023

Explore 7T96 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7T96 contains 31 α-helices and 60 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: 14 helices, 0 β-strands

Element	Residues	Length
α-helix	23-49	27
α-helix	52-54	3
α-helix	57-72	16
α-helix	75-84	10
α-helix	92-94	3
α-helix	96-126	31
α-helix	131-134	4
α-helix	137-166	30
α-helix	184-191	8
α-helix	192-196	5
α-helix	197-211	15
α-helix	381-410	30
α-helix	421-441	21
α-helix	447-456	10

Chain B: 9 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	9-30	22
β-strand	33-39	7	1
α-helix	46-51	6
β-strand	186-191	6	1
β-strand	196-201	6	1
α-helix	209-211	3
α-helix	213-216	4
β-strand	221-227	7	1
β-strand	233	1	2
β-strand	242	1	2
α-helix	243-255	13
β-strand	264-270	7	1
α-helix	274-281	8
α-helix	284-286	3
α-helix	297-309	13
β-strand	319-322	4	1
α-helix	332-351	20

Chain C: 3 helices, 29 β-strands

Element	Residues	Length	Sheet
α-helix	4-25	22
α-helix	30-33	4
α-helix	38-39	2
β-strand	47-51	5	3
β-strand	58-63	6	4
β-strand	69-74	6	4
β-strand	78-83	6	4
β-strand	88-94	7	4
β-strand	100-105	6	5
β-strand	111-116	6	5
β-strand	121-125	5	5
β-strand	135-139	5	5
β-strand	146-153	8	6
β-strand	156-161	6	6
β-strand	165-168	4	6
β-strand	178-181	4	6
β-strand	187	1	7
β-strand	191-192	2	7
β-strand	199-203	5	7
β-strand	207-210	4	7
β-strand	220-222	3	7
β-strand	229-234	6	8
β-strand	240-245	6	8
β-strand	250-254	5	8
β-strand	260-264	5	8
β-strand	273-278	6	9
β-strand	284-289	6	9
β-strand	293-298	6	9
β-strand	304-309	6	9
β-strand	315-320	6	3
β-strand	327-331	5	3
β-strand	336-339	4	3

Chain D: 2 helices, 0 β-strands

Element	Residues	Length	Sheet
α-helix	8-22	15
α-helix	30-43	14

Chain E: 3 helices, 23 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	10
β-strand	10-12	3	11
β-strand	17-25	9	10
α-helix	29-31	3
β-strand	34-39	6	11
β-strand	45-51	7	11
β-strand	58-60	3	11
β-strand	69-73	5	10
β-strand	78-84	7	10
α-helix	88-90	3
β-strand	92-98	7	11
β-strand	111	1	11
β-strand	115-119	5	11
β-strand	141	1	12
β-strand	146-149	4	13
β-strand	154-160	7	12
β-strand	166	1	14
β-strand	172	1	14
β-strand	174-179	6	13
β-strand	186-190	5	13
β-strand	194-195	2	13
β-strand	204-208	5	12
β-strand	211-217	7	12
β-strand	226-231	6	13
α-helix	237	1
β-strand	243-247	5	13

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Muscarinic acetylcholine receptor M2	A	protein	353	Homo sapiens	P08172 (AlphaFold model)
Guanine nucleotide-binding protein G(o) subunit alpha	B	protein	354	Homo sapiens	P09471 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	C	protein	345	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	D	protein	71	Homo sapiens	P59768 (AlphaFold model)
scFV16	E	protein	256	Mus musculus

Sequence of entity 1 (A), FASTA

>7T96_1 Muscarinic acetylcholine receptor M2 (chains A)
DYKDDDDASTDSSDNSLALTSPYKTFEVVFIVLVAGSLSLVTIIGNILVMVSIKVNRHLQ
TVNNYFLFSLACADLIIGVFSMNLYTLYTVIGYWPLGPVVCDLWLALDYVVSNASVMNLL
IISFDRYFCVTKPLTYPVKRTTKMAGMMIAAAWVLSFILWAPAILFWQFIVGVRTVEDGE
CYIQFFSNAAVTFGTAIAAFYLPVIIMTVLYWHISRASKSRIKKDKKEPVANQDPVSIVA
RKIVKMTKQPAKKKPPPSREKKVTRTILAILLAFIITWAPYNVMVLINTFCAPCIPNTVW
TIGYWLCYINSTINPACYALCNATFKKTFKHLLMCHYKNIGATRPAGLEVLFQ

Sequence of entity 2 (B), FASTA

>7T96_2 Guanine nucleotide-binding protein G(o) subunit alpha (chains B)
MGCTLSAEDKAAVERSKMIEKNLKEDGISAAKDVKLLLLGAGESGKSTIVKQMKIIHEDG
FSGEDVKQYKPVVYSNTIQSLAAIVRAMDTLGIEYGDKERKADAKMVCDVVSRMEDTEPF
SAELLSAMMRLWGDSGIQECFNRSREYQLNDSAKYYLDSLDRIGAADYQPTEQDILRTRV
KTTGIVETHFTFKNLHFRLFDVGGQRSERKKWIHCFEDVTAIIFCVALSGYDQVLHEDET
TNRMHESLMLFDSICNNKFFIDTSIILFLNKKDLFGEKIKKSPLTICFPEYTGPNTYEDA
AAYIQAQFESKNRSPNKEIYCHMTCATDTNNIQVVFDAVTDIIIANNLRGCGLY

Sequence of entity 3 (C), FASTA

>7T96_3 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains C)
GPGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHL
AKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACG
GLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQ
QTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFF
PNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCN
VWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 4 (D), FASTA

>7T96_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains D)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 5 (E), FASTA

>7T96_5 scFV16 (chains E)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELKGSLEVLFQ

Ligands and cofactors

ID	Name	Formula	Copies
2CU	3-amino-5-chloro-N-cyclopropyl-4-methyl-6-[2-(4-methylpiperazin-1-yl)-2-oxoetho…	C19 H24 Cl N5 O3 S	1
ACH	Acetylcholine	C7 H16 N O2	1

Primary citation

Structural and dynamic insights into supra-physiological activation and allosteric modulation of a muscarinic acetylcholine receptor. Xu, J., Wang, Q., Hubner, H. et al. Nat Commun (2023) 14:376-376. DOI 10.1038/s41467-022-35726-z · PubMed

Other PDB entries of the same protein (UniProt P08172 (AlphaFold model), which also has an AlphaFold model), best resolution first:

5ZKC 2.3 Å, Crystal structure of rationally thermostabilized M2 muscarinic acetylcholine receptor…
5YC8 2.5 Å, Crystal structure of rationally thermostabilized M2 muscarinic acetylcholine receptor…
5ZK3 2.6 Å, Crystal structure of rationally thermostabilized M2 muscarinic acetylcholine receptor…
8J8R 2.9 Å, Structure of beta-arrestin2 in complex with M2Rpp
5ZKB 2.95 Å, Crystal structure of rationally thermostabilized M2 muscarinic acetylcholine receptor…
3UON 3.0 Å, Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist
5ZK8 3.0 Å, Crystal structure of M2 muscarinic acetylcholine receptor bound with NMS
8JAF 3.1 Å, Structure of Muscarinic receptor (M2R) in complex with beta-arrestin1 (Local Refine,…
7T94 3.16 Å, Cryo-EM structure of S1 state ACh-bound M2R-Go signaling complex with a PAM
8J97 3.2 Å, Structure of Muscarinic receptor (M2R) in complex with beta-arrestin1 (Local refine,…
7T8X 3.21 Å, Cryo-EM structure of ACh-bound M2R-Go signaling complex in S1 state
7T90 3.32 Å, Cryo-EM structure of ACh-bound M2R-Go signaling complex in S2 state

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