7T90: ACh-bound M2R-Go signaling complex in S2 state

Cryo-EM structure of ACh-bound M2R-Go signaling complex in S2 state. Determined by electron microscopy at 3.32 Å resolution. Released 25 Jan 2023.

Method: Electron microscopy
Resolution: 3.32 Å
Organisms: Homo sapiens, Mus musculus
Chains: 5
Atoms: 8,451
Mol. weight: 152.91 kDa
Ligands: ACH
Released: 25 Jan 2023

Explore 7T90 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7T90 contains 35 α-helices and 64 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: 16 helices, 0 β-strands

Element	Residues	Length
α-helix	23-50	28
α-helix	57-59	3
α-helix	60-86	27
α-helix	92-126	35
α-helix	131-134	4
α-helix	137-161	25
α-helix	162-164	3
α-helix	179-182	4
α-helix	186-191	6
α-helix	192-196	5
α-helix	197-213	17
α-helix	382-412	31
α-helix	422-430	9
α-helix	432-437	6
α-helix	438-442	5
α-helix	445-455	11

Chain B: 9 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	10-30	21
β-strand	33-39	7	1
α-helix	46-50	5
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	265-270	6	1
α-helix	272-278	7
α-helix	284-286	3
α-helix	297-309	13
β-strand	319-324	6	1
α-helix	330-351	22

Chain C: 2 helices, 29 β-strands

Element	Residues	Length	Sheet
α-helix	4-25	22
α-helix	30-33	4
β-strand	47-52	6	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	103-105	3	5
β-strand	111-114	4	5
β-strand	121-125	5	5
β-strand	134-139	6	5
β-strand	146-151	6	6
β-strand	156-161	6	6
β-strand	165-170	6	6
β-strand	176-181	6	6
β-strand	187	1	7
β-strand	191-192	2	7
β-strand	198-203	6	7
β-strand	207-212	6	7
β-strand	218-221	4	7
β-strand	229-234	6	8
β-strand	240-245	6	8
β-strand	250-254	5	8
β-strand	259-264	6	8
β-strand	273-277	5	9
β-strand	284-289	6	9
β-strand	294-298	5	9
β-strand	304	1	9
β-strand	315-320	6	3
β-strand	327-331	5	3
β-strand	335-339	5	3

Chain D: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	8-22	15
α-helix	30-43	14
α-helix	53-55	3
α-helix	56-58	3

Chain E: 4 helices, 27 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	10
β-strand	10-12	3	11
β-strand	18-25	8	10
α-helix	29-31	3
β-strand	34-39	6	12
β-strand	45-51	7	12
α-helix	53-55	3
β-strand	58-60	3	12
β-strand	69-73	5	10
α-helix	74-76	3
β-strand	78-83	6	10
α-helix	88-90	3
β-strand	93	1	12
β-strand	94	1	13
β-strand	97	1	14
β-strand	111	1	14
β-strand	115	1	13
β-strand	117-119	3	11
β-strand	141-142	2	15
β-strand	146-148	3	16
β-strand	155-160	6	15
β-strand	166	1	17
β-strand	172	1	17
β-strand	174-179	6	16
β-strand	185-190	6	16
β-strand	194-195	2	16
β-strand	204-208	5	15
β-strand	211-216	6	15
β-strand	225-227	3	16
β-strand	229-231	3	16
β-strand	243-246	4	16

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

>7T90_1 Muscarinic acetylcholine receptor M2 (chains A)
DYKDDDDASTDSSDNSLALTSPYKTFEVVFIVLVAGSLSLVTIIGNILVMVSIKVNRHLQ
TVNNYFLFSLACADLIIGVFSMNLYTLYTVIGYWPLGPVVCDLWLALDYVVSNASVMNLL
IISFDRYFCVTKPLTYPVKRTTKMAGMMIAAAWVLSFILWAPAILFWQFIVGVRTVEDGE
CYIQFFSNAAVTFGTAIAAFYLPVIIMTVLYWHISRASKSRIKKDKKEPVANQDPVSIVA
RKIVKMTKQPAKKKPPPSREKKVTRTILAILLAFIITWAPYNVMVLINTFCAPCIPNTVW
TIGYWLCYINSTINPACYALCNATFKKTFKHLLMCHYKNIGATRPAGLEVLFQ

Sequence of entity 2 (B), FASTA

>7T90_2 Guanine nucleotide-binding protein G(o) subunit alpha (chains B)
MGCTLSAEDKAAVERSKMIEKNLKEDGISAAKDVKLLLLGAGESGKSTIVKQMKIIHEDG
FSGEDVKQYKPVVYSNTIQSLAAIVRAMDTLGIEYGDKERKADAKMVCDVVSRMEDTEPF
SAELLSAMMRLWGDSGIQECFNRSREYQLNDSAKYYLDSLDRIGAADYQPTEQDILRTRV
KTTGIVETHFTFKNLHFRLFDVGGQRSERKKWIHCFEDVTAIIFCVALSGYDQVLHEDET
TNRMHESLMLFDSICNNKFFIDTSIILFLNKKDLFGEKIKKSPLTICFPEYTGPNTYEDA
AAYIQAQFESKNRSPNKEIYCHMTCATDTNNIQVVFDAVTDIIIANNLRGCGLY

Sequence of entity 3 (C), FASTA

>7T90_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

>7T90_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains D)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 5 (E), FASTA

>7T90_5 scFV16 (chains E)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELKGSLEVLFQ

Ligands and cofactors

ID	Name	Formula	Copies
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
7T96 3.22 Å, Cryo-EM structure of S2 state ACh-bound M2R-Go signaling complex with a PAM

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