8THL: Epinephrine-bound alpha-1A-adrenergic receptor

Cryo-EM structure of epinephrine-bound alpha-1A-adrenergic receptor in complex with heterotrimeric Gq-protein. Determined by electron microscopy at 3.1 Å resolution. Released 16 Aug 2023.

Method: Electron microscopy
Resolution: 3.1 Å
Organisms: Homo sapiens, Enterobacteria phage T4
Chains: 5
Atoms: 7,837
Mol. weight: 160.7 kDa
Ligands: ALE
Released: 16 Aug 2023

Explore 8THL in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8THL contains 35 α-helices and 58 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: 10 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	8-30	23
β-strand	34-39	6	1
α-helix	46-48	3
β-strand	69-76	8	1
β-strand	79-86	8	1
α-helix	96-100	5
β-strand	105-111	7	1
α-helix	118-129	12
α-helix	132-134	3
β-strand	138-144	7	1
α-helix	146-155	10
α-helix	160-163	4
α-helix	165-167	3
α-helix	184-202	19
β-strand	215-216	2	1
α-helix	223-242	20

Chain B: 4 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	4-24	21
α-helix	30-33	4
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	88-94	7	3
β-strand	102-105	4	4
β-strand	111-115	5	4
β-strand	120-125	6	4
β-strand	134-140	7	4
β-strand	146-153	8	5
β-strand	156-161	6	5
β-strand	165-168	4	5
β-strand	178-181	4	5
β-strand	187-192	6	6
β-strand	198-203	6	6
β-strand	208-212	5	6
β-strand	217-222	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
β-strand	273-278	6	8
β-strand	284-289	6	8
β-strand	293-298	6	8
β-strand	304-309	6	8
β-strand	318-320	3	2
β-strand	327-329	3	2
β-strand	336-339	4	2

Chain F: 3 helices, 24 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
α-helix	53-55	3
β-strand	58-60	3	10
β-strand	68-73	6	9
β-strand	78-84	7	9
β-strand	92-99	8	10
β-strand	111-119	9	10
β-strand	128-129	2	11
β-strand	135-136	2	12
β-strand	143-147	5	13
β-strand	148-149	2	11
β-strand	154	1	14
β-strand	160	1	14
β-strand	162-167	6	12
β-strand	174-178	5	12
β-strand	182-183	2	12
α-helix	184	1
β-strand	191-196	6	13
β-strand	199-204	6	13
β-strand	213-219	7	12
β-strand	227	1	12
β-strand	231-234	4	12

Chain G: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	10-23	14
α-helix	30-43	14
α-helix	45-47	3
α-helix	54-55	2

Chain R: 14 helices, 0 β-strands

Element	Residues	Length
α-helix	34-53	20
α-helix	60-89	30
α-helix	96-100	5
α-helix	102-129	28
α-helix	134-137	4
α-helix	143-162	20
α-helix	167-170	4
α-helix	182-189	8
α-helix	190-194	5
α-helix	195-213	19
α-helix	269-285	17
α-helix	288-297	10
α-helix	299-301	3
α-helix	305-325	21

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(i) subunit alpha-2,Guanine nucleotide-binding protein G(s)…	A	protein	246	Homo sapiens	P04899 (AlphaFold model), P50148 (AlphaFold model), P63092 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	358	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	71	Homo sapiens	P59768
Single fab chain (scFv16)	F	protein	267	Homo sapiens
Endolysin,Alpha-1A adrenergic receptor	R	protein	503	Enterobacteria phage T4, Homo sapiens	P00720, P35348

Sequence of entity 1 (A), FASTA

>8THL_1 Guanine nucleotide-binding protein G(i) subunit alpha-2,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short,Guanine nucleotide-binding protein G(q) subunit alpha (chains A)
MGSTVSAEDKAAAERSKMIDKNLREDGEKARRTLRLLLLGADNSGKSTIVKQMRILHGGS
GGSGGTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTAIIFVVDSSDYNRLQE
ALNDFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEP
GEDPRVTRAKYFIRKEFVDISTASGDGRHICYPHFTCAVDTENARRIFNDCKDIILQMNL
REYNLV

Sequence of entity 2 (B), FASTA

>8THL_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MHHHHHHLEVLFQGPGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGR
IQMRTRRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMT
CAYAPSGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSG
DTTCALWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTF
TGHESDINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSG
RLLLAGYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (G), FASTA

>8THL_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (F), FASTA

>8THL_4 Single fab chain (scFv16) (chains F)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELKAAALEVLFQGPHHHHHHHH

Sequence of entity 5 (R), FASTA

>8THL_5 Endolysin,Alpha-1A adrenergic receptor (chains R)
MKTIIALSYIFCLVFADYKDDDDKNIFEMLRIDEGLRLKIYKDTEGYYTIGIGHLLTKSP
SLNAAKSELDKAIGRNTNGVITKDEAEKLFNQDVDAAVRGILRNAKLKPVYDSLDAVRRA
ALINMVFQMGETGVAGFTNSLRMLQQKRWDEAAVNLAKSRWYNQTPNRAKRVITTFRTGT
WDAYAAATQPPAPVNISKAILLGVILGGLILFGVLGNILVILSVACHRHLHSVTHYYIVN
LAVADLLLTSTVLPFSAIFEVLGYWAFGRVFCNIWAAVDVLCCTASIMGLCIISIDRYIG
VSYPLRYPTIVTQRRGLMALLCVWALSLVISIGPLFGWRQPAPEDETICQINEEPGYVLF
SALGSFYLPLAIILVMYCRVYVVAKRESRGLKSGLKTDKSHFSVRLLKFSREKKAAKTLG
IVVGCFVLCWLPFFLVMPIGSFFPDFKPSETVFKIVFWLGYLNSCINPIIYPCSSQEFKK
AFQNVLRIQCLCRKQASLEVLFQ

Ligands and cofactors

ID	Name	Formula	Copies
ALE	L-epinephrine	C9 H13 N O3	1

Primary citation

Structural basis of agonist specificity of alpha 1A -adrenergic receptor. Su, M., Wang, J., Xiang, G. et al. Nat Commun (2023) 14:4819-4819. DOI 10.1038/s41467-023-40524-2 · PubMed

Other PDB entries of the same protein (UniProt P04899 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8ZBW 2.58 Å, Cryo-EM structure of formyl peptide receptor 2/C1R receptor in complex with Gi
8THK 2.6 Å, Cryo-EM structure of A61603-bound alpha-1A-adrenergic receptor in complex with…
7YK7 2.75 Å, Cryo-EM structure of the DC591053-bound human relaxin family peptide receptor 4…
9K6L 2.77 Å, Cryo-EM structure of GPCR16-Gi2 complex
9XDQ 2.79 Å, Cryo-EM structure of BMS986187 bound DOR-Gi complex
7WVX 2.8 Å, Cryo-EM structure of the human formyl peptide receptor 2 in complex with fhumanin and Gi2
8W8A 2.8 Å, Cryo-EM structure of the RO5256390-TAAR1 complex
8ZSJ 2.8 Å, Cryo-EM structure of the apo hTAAR1-Gs complex
7WVV 2.9 Å, Cryo-EM structure of the human formyl peptide receptor 2 in complex with fMLFII and Gi2
9DQJ 2.9 Å, CryoEM structure of Gq-coupled MRGPRD with a new agonist EP-3945
9KFI 2.91 Å, Cryo-EM structure of the human relaxin family peptide receptor 3 in complex with…
9KFK 2.95 Å, Cryo-EM structure of the relaxin-3-bound human relaxin family peptide receptor 4…

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