8HAF: PTHrP-PTH1R-Gs complex

PTHrP-PTH1R-Gs complex. Determined by electron microscopy at 3.25 Å resolution. Released 21 Dec 2022.

Method: Electron microscopy
Resolution: 3.25 Å
Organisms: Bos taurus, Rattus norvegicus, Lama glama
Chains: 6
Atoms: 9,681
Mol. weight: 172.71 kDa
Ligands: PLM, CLR
Released: 21 Dec 2022

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

Secondary structure: helices and β-sheets

8HAF contains 35 α-helices and 47 β-strands across 6 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, 6 β-strands

Element	Residues	Length	Sheet
α-helix	6-32	27
β-strand	34-40	7	1
α-helix	46-55	10
β-strand	208-214	7	1
β-strand	217-223	7	1
α-helix	236-240	5
β-strand	243-249	7	1
α-helix	266-278	13
β-strand	286-292	7	1
α-helix	294-303	10
α-helix	313-317	5
α-helix	332-351	20
β-strand	359-363	5	1
α-helix	371-390	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	46-52	7	2
β-strand	58-63	6	3
β-strand	69-74	6	3
β-strand	78-83	6	3
β-strand	89-94	6	3
β-strand	100-105	6	4
β-strand	111-116	6	4
β-strand	121-125	5	4
β-strand	134-139	6	4
β-strand	146-151	6	5
β-strand	156-161	6	5
β-strand	165-170	6	5
β-strand	176-181	6	5
β-strand	187-192	6	6
β-strand	198-203	6	6
β-strand	208-212	5	6
β-strand	218-222	5	6
β-strand	229-234	6	7
β-strand	240-245	6	7
β-strand	250-254	5	7
β-strand	260-264	5	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	315-320	6	2
β-strand	327-331	5	2
β-strand	335-340	6	2

Chain G: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	8-23	16
α-helix	30-43	14
α-helix	53-55	3

Chain N: 3 helices, 13 β-strands

Element	Residues	Length	Sheet
β-strand	3	1	9
β-strand	6-7	2	10
β-strand	10-12	3	11
β-strand	17-23	7	10
β-strand	25	1	9
α-helix	29-31	3
β-strand	34-39	6	11
β-strand	45-51	7	11
β-strand	58-60	3	11
α-helix	62-64	3
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	118	1	11
β-strand	122-126	5	11

Chain P: 2 helices, 0 β-strands

Element	Residues	Length	Sheet
α-helix	6-31	26
α-helix	33-35	3

Chain R: 15 helices, 0 β-strands

Element	Residues	Length
α-helix	34-50	17
α-helix	127-129	3
α-helix	168-171	4
α-helix	179-211	33
α-helix	218-243	26
α-helix	279-307	29
α-helix	308-312	5
α-helix	317-320	4
α-helix	321-346	26
α-helix	358-360	3
α-helix	361-392	32
α-helix	400-413	14
α-helix	435-456	22
α-helix	457-461	5
α-helix	464-479	16

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(s) subunit alpha-1	A	protein	361	Bos taurus
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	400	Rattus norvegicus	P54311 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	71	Bos taurus	P63212 (AlphaFold model)
Nanobody 35	N	protein	140	Lama glama
PTHrP[1-36]	P	protein	37	synthetic construct	P12272 (AlphaFold model)
Parathyroid hormone/parathyroid hormone-related peptide receptor	R	protein	476	Homo sapiens	Q03431 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8HAF_1 Guanine nucleotide-binding protein G(s) subunit alpha-1 (chains A)
MGCTLSAEDKAAVERSKMIEKQLQKDKQVYRATHRLLLLGADNSGKSTIVKQMRIYHVNG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TSGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFNDVTAIIFVVDSSDYNRLQEALNDF
KSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEPGEDPR
VTRAKYFIRDEFLRISTASGDGRHYCYPHFTCSVDTENARRIFNDCRDIIQRMHLRQYEL
L

Sequence of entity 2 (B), FASTA

>8HAF_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MHHHHHHSSGLVPRGSHMASHHHHHHHHHHGSLLQSELDQLRQEAEQLKNQIRDARKACA
DATLSQITNNIDPVGRIQMRTRRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYT
TNKVHAIPLRSSWVMTCAYAPSGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYL
SCCRFLDDNQIVTSSGDTTCALWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDA
SAKLWDVREGMCRQTFTGHESDINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSH
DNIICGITSVSFSKSGRLLLAGYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMA
VATGSWDSFLKIWNGSSGGGGSGGGGSSGVSGWRLFKKIS

Sequence of entity 3 (G), FASTA

>8HAF_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (N), FASTA

>8HAF_4 Nanobody 35 (chains N)
MAQVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASI
SYTGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYR
GQGTQVTVSSHHHHHHEPEA

Sequence of entity 5 (P), FASTA

>8HAF_5 PTHrP[1-36] (chains P)
AVSEHQLLHDKGKSIQDLRRRFFLHHLIAEIHTAEIX

Sequence of entity 6 (R), FASTA

>8HAF_6 Parathyroid hormone/parathyroid hormone-related peptide receptor (chains R)
DADDVMTKEEQIFLLHRAQAQCEKRLKEVLQRPASIMESDKGWTSASTSGKPRKDKASGK
LYPESEEDKEAPTGSRYRGRPCLPEWDHILCWPLGAPGEVVAVPCPDYIYDFNHKGHAYR
RCDRNGSWELVPGHNRTWANYSECVKFLTNETREREVFDRLAMIYTVGYSVSLASLTVAV
LILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAERLTEEELRAIAQ
APPPPATAAAGYAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTV
FGWGLPAVFVAVWVSVRATLANTGCWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLA
TKLRETNAGRCDTRQQYRKLLKSTLVLMPLFGVHYIVFMATPYTEVSGTLWQVQMHYEML
FNSFQGFFVAIIYCFCNGEVQAEIKKSWSRWTLALDFRRKARSGSSSYSYGPMVSH

Ligands and cofactors

ID	Name	Formula	Copies
PLM	Palmitic acid	C16 H32 O2	11
CLR	Cholesterol	C27 H46 O	6

Primary citation

Molecular recognition of two endogenous hormones by the human parathyroid hormone receptor-1. Zhao, L.H., Yuan, Q.N., Dai, A.T. et al. Acta Pharmacol Sin (2023) 44:1227-1237. DOI 10.1038/s41401-022-01032-z · PubMed

Other PDB entries of the same protein (UniProt P54311 (AlphaFold model), which also has an AlphaFold model), best resolution first:

7MBX 1.95 Å, Human Cholecystokinin 1 receptor (CCK1R) Gs complex
9EJZ 2.06 Å, Human M5 muscarinic acetylcholine receptor complex with mini-Gq, agonist acetylcholine…
9IJE 2.34 Å, Epinephrine-activated human beta3 adrenergic receptor
8YK0 2.4 Å, Cryo-EM structure of human GPR156-Gi3 complex
8Z9O 2.4 Å, Cryo-EM structure of human GPR4-Gs complex
22ES 2.43 Å, Gi bound kappa-opioid receptor in complex with difelikefalin
7MBY 2.44 Å, Human Cholecystokinin 1 receptor (CCK1R) Gq chimera (mGsqi) complex
9WG6 2.44 Å, D1R-Gs in complexed with Dopamine/LY3154207/BMSA1/UNC9815
8JIS 2.46 Å, Cryo-EM structure of the GLP-1R/GCGR dual agonist peptide15-bound human GLP-1R-Gs complex
9M0R 2.47 Å, Structure of neuropeptide FF receptor 1 complex with NPVF
8YKV 2.48 Å, Cryo-EM structure of succinate receptor SUCR1 bound to compound 31
9M1O 2.49 Å, Cryo-EM structures of NPFFR2 complex with neuropeptide FF

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