9PLO: Alpha2a adrenergic receptor

Structure of alpha2a adrenergic receptor in complex with Go heterotrimer, scFv16, and N-(5-methylnaphthalen-1-yl)pyridin-4-amine (compound 4905). Determined by electron microscopy at 2.8 Å resolution. Released 30 Jul 2025.

Method: Electron microscopy
Resolution: 2.8 Å
Organisms: Homo sapiens, Mus musculus
Chains: 5
Atoms: 8,635
Mol. weight: 172.41 kDa
Ligands: A1CIU
Released: 30 Jul 2025

Explore 9PLO in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9PLO contains 37 α-helices and 63 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: 9 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	7-31	25
β-strand	34-38	5	1
α-helix	46-52	7
β-strand	186-191	6	1
β-strand	196-201	6	1
α-helix	214-216	3
β-strand	221-227	7	1
α-helix	228-232	5
β-strand	234	1	2
β-strand	242	1	2
α-helix	243-255	13
β-strand	265-270	6	1
α-helix	272-279	8
α-helix	284-286	3
α-helix	297-310	14
β-strand	319-323	5	1
α-helix	331-350	20

Chain B: 3 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	7-24	18
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	134-139	6	5
β-strand	146-153	8	6
β-strand	156-161	6	6
β-strand	165-170	6	6
β-strand	175-181	7	6
β-strand	187-192	6	7
β-strand	198-203	6	7
β-strand	208-212	5	7
β-strand	218-222	5	7
β-strand	232-234	3	8
β-strand	240-243	4	8
β-strand	250-254	5	8
β-strand	259-264	6	8
β-strand	273-278	6	9
β-strand	284-289	6	9
β-strand	294-298	5	9
β-strand	304-308	5	9
β-strand	317-320	4	3
β-strand	327-330	4	3
β-strand	336-339	4	3

Chain G: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	10-23	14
α-helix	30-45	16
α-helix	53-55	3

Chain R: 15 helices, 0 β-strands

Element	Residues	Length
α-helix	47-75	29
α-helix	77-79	3
α-helix	84-96	13
α-helix	97-101	5
α-helix	102-110	9
α-helix	118-120	3
α-helix	121-150	30
α-helix	153-158	6
α-helix	162-180	19
α-helix	209-216	8
α-helix	217-221	5
α-helix	222-242	21
α-helix	377-414	38
α-helix	422-443	22
α-helix	446-456	11

Chain S: 7 helices, 27 β-strands

Element	Residues	Length	Sheet
β-strand	3-6	4	10
β-strand	11-12	2	11
β-strand	18-25	8	10
α-helix	29-31	3
β-strand	33-39	7	12
β-strand	46-51	6	12
β-strand	58-60	3	12
β-strand	68-73	6	10
α-helix	74-76	3
β-strand	78-83	6	10
α-helix	88-90	3
β-strand	92-99	8	12
β-strand	110-111	2	12
β-strand	115-117	3	12
β-strand	118-119	2	11
β-strand	129	1	13
β-strand	134-136	3	14
β-strand	143	1	15
β-strand	146-148	3	13
β-strand	154	1	16
β-strand	160	1	16
β-strand	162-167	6	14
β-strand	174-178	5	14
β-strand	182-183	2	14
α-helix	184	1
β-strand	192-195	4	13
β-strand	199-203	5	13
β-strand	204	1	15
α-helix	209-211	3
β-strand	214-219	6	14
α-helix	225	1
β-strand	226-227	2	14
α-helix	228-230	3
β-strand	231-234	4	14

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(o) subunit alpha	A	protein	354	Homo sapiens	P09471 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	370	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	71	Homo sapiens	P59768 (AlphaFold model)
Alpha-2A adrenergic receptor	R	protein	491	Homo sapiens	P08913 (AlphaFold model)
scFv16	S	protein	279	Mus musculus

Sequence of entity 1 (A), FASTA

>9PLO_1 Guanine nucleotide-binding protein G(o) subunit alpha (chains A)
MGCTLSAEERAALERSKAIEKNLKEDGISAAKDVKLLLLGAGESGKSTIVKQMKIIHEDG
FSGEDVKQYKPVVYSNTIQSLAAIVRAMDTLGIEYGDKERKADAKMVCDVVSRMEDTEPF
SAELLSAMMRLWGDSGIQECFNRSREYQLNDSAKYYLDSLDRIGAADYQPTEQDILRTRV
KTTGIVETHFTFKNLHFRLFDVGGQRSERKKWIHCFEDVTAIIFCVALSGYDQVLHEDET
TNRMHESLMLFDSICNNKFFIDTSIILFLNKKDLFGEKIKKSPLTICFPEYTGPNTYEDA
AAYIQAQFESKNRSPNKEIYCHMTCATDTNNIQVVFDAVTDIIIANNLRGCGLY

Sequence of entity 2 (B), FASTA

>9PLO_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MHHHHHHLEVLFQGPEDQVDPRLIDGKGSSGSELDQLRQEAEQLKNQIRDARKACADATL
SQITNNIDPVGRIQMRTRRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKV
HAIPLRSSWVMTCAYAPSGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCR
FLDDNQIVTSSGDTTCALWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKL
WDVREGMCRQTFTGHESDINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNII
CGITSVSFSKSGRLLLAGYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATG
SWDSFLKIWN

Sequence of entity 3 (G), FASTA

>9PLO_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (R), FASTA

>9PLO_4 Alpha-2A adrenergic receptor (chains R)
MKTIIALSYIFCLVFADYKDDDDASIDFRQEQPLAEGSFAPMGSLQPDAGNASWNGTEAP
GGGARATPYSLQVTLTLVCLAGLLMLLTVFGNVLVIIAVFTSRALKAPQNLFLVSLASAD
ILVATLVIPFSLANEVMGYWYFGKAWCEIYLALDVLFCTSSIVHLCAISLDRYWSITQAI
EYNLKRTPRRIKAIIITVWVISAVISFPPLISIEKKGGGGGPQPAEPRCEINDQKWYVIS
SCIGSFFAPCLIMILVYVRIYQIAKRRTRVPPSRRGPDAVAAPPGGTERRPNGLGPERSA
GPGGAEAEPLPTQLNGAPGEPAPAGPRDTDALDLEESSSSDHAERPPGPRRPERGPRGKG
KARASQVKPGDSLPRRGPGATGIGTPAAGPGEERVGAAKASRWRGRQNREKRFTFVLAVV
IGVFVVCWFPFFFTYTLTAVGCSVPRTLFKFFFWFGYCNSSLNPVIYTIFNHDFRRAFKK
ILCRGDRKRIV

Sequence of entity 5 (S), FASTA

>9PLO_5 scFv16 (chains S)
MVSAIVLYVLLAAAAHSAFADVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQA
PEKGLEWVAYISSGSGTIYYADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSI
YYYGSSPFDFWGQGTTLTVSSGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCR
SSKSLLHSNGNTYLYWFLQRPGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLE
AEDVGVYYCMQHLEYPLTFGAGTKLELKAAAHHHHHHHH

Ligands and cofactors

ID	Name	Formula	Copies
A1CIU	N-(5-methylnaphthalen-1-yl)pyridin-4-amine	C16 H14 N2	1

Primary citation

Development of a random background to understand ligand optimization. Xu, X., Mailhot, O., Correy, G.J. et al. Nature (2026). DOI 10.1038/s41586-026-11013-5 · PubMed

Other PDB entries of the same protein (UniProt P09471 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9BSB 2.32 Å, Global reconstruction of DRD2 bound to LSD in complex with a mini-GoA and scFv16…
9VJE 2.47 Å, Cryo-EM structure of 5-HT1AR-GoA in complex with buspirone
9K20 2.65 Å, Cryo-EM structure of ATP-bound P2Y purinoceptor 2-miniGo-scFv16 complex
9VJ5 2.69 Å, Cryo-EM structure of 5-HT1AR-GoA in complex with gepirone
8E9X 2.7 Å, CryoEM structure of miniGo-coupled hM4Di in complex with DCZ
9T88 2.74 Å, Cryo-EM structure of ESG-2-37-bound D3 dopamine receptor with mini-Go
9VNF 2.74 Å, Cryo-EM structure of 5-HT1AR-GoA in complex with (S)-pindolol
8YN7 2.77 Å, Cryo-EM structure of histamine H3 receptor in complex with immethridine and miniGo
8YN8 2.77 Å, Cryo-EM structure of histamine H3 receptor in complex with proxyfan and miniGo
9KVP 2.79 Å, Structure of SB290157 bound to human C3aR in complex with Go (Full map)
7W2Z 2.8 Å, Cryo-EM structure of the ghrelin-bound human ghrelin receptor-Go complex
8XXH 2.8 Å, Structure of CXCR2 bound to CXCL2 (CXCR2-CXCL2-Go Full map)

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