6NBI: Parathyroid hormone receptor type 1

Cryo-EM structure of parathyroid hormone receptor type 1 in complex with a long-acting parathyroid hormone analog and G protein. Determined by electron microscopy at 4.0 Å resolution. Released 17 Apr 2019.

Method: Electron microscopy
Resolution: 4.0 Å
Organisms: Homo sapiens, Bos taurus, Rattus norvegicus
Chains: 6
Atoms: 9,195
Mol. weight: 163.54 kDa
Ligands: CLR
Released: 17 Apr 2019

Explore 6NBI in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

6NBI contains 36 α-helices and 53 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	12-39	28
β-strand	41-47	7	5
β-strand	207-213	7	5
β-strand	218-224	7	5
α-helix	234-237	4
β-strand	243-249	7	5
α-helix	265-278	14
α-helix	280-282	3
β-strand	286-292	7	5
α-helix	294-299	6
α-helix	325-327	3
α-helix	332-349	18
β-strand	359-363	5	5
α-helix	371-390	20

Chain B: 2 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	5-25	21
β-strand	47-51	5	6
β-strand	58-63	6	7
β-strand	69-74	6	7
β-strand	78-83	6	7
β-strand	89-94	6	7
β-strand	102-105	4	8
β-strand	111-115	5	8
β-strand	121-125	5	8
β-strand	135-139	5	8
β-strand	146-151	6	9
β-strand	156-161	6	9
β-strand	165-170	6	9
β-strand	176-181	6	9
β-strand	187-192	6	10
β-strand	198-203	6	10
β-strand	208-212	5	10
β-strand	218-222	5	10
β-strand	229-234	6	11
β-strand	240-245	6	11
β-strand	250-254	5	11
β-strand	260-264	5	11
α-helix	272	1
β-strand	273-278	6	12
β-strand	284-289	6	12
β-strand	294-298	5	12
β-strand	304-308	5	12
β-strand	315-320	6	6
β-strand	327-331	5	6
β-strand	336-339	4	6

Chain G: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	7-23	17
α-helix	30-43	14
α-helix	53-55	3

Chain N: 3 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	13
β-strand	10-11	2	14
β-strand	17-25	9	13
α-helix	29-31	3
β-strand	34-39	6	14
β-strand	45-51	7	14
β-strand	58-60	3	14
α-helix	62-64	3
β-strand	68-73	6	13
β-strand	78-84	7	13
α-helix	88-90	3
β-strand	92-98	7	14
β-strand	118	1	14
β-strand	122-125	4	14

Chain P: 2 helices, 0 β-strands

Element	Residues	Length	Sheet
α-helix	3-15	13
α-helix	18-24	7

Chain R: 18 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	33-52	20
α-helix	107	1
β-strand	108	1	1
α-helix	109-110	2
β-strand	112	1	2
β-strand	117	1	2
β-strand	121	1	1
α-helix	122	1
β-strand	126-130	5	3
α-helix	131-132	2
β-strand	143-147	5	3
β-strand	148	1	4
β-strand	154	1	4
α-helix	174-200	27
α-helix	204-211	8
α-helix	219-249	31
α-helix	274-312	39
α-helix	317-346	30
α-helix	358-360	3
α-helix	361-368	8
α-helix	372-394	23
α-helix	400-411	12
α-helix	420-423	4
α-helix	435-456	22
α-helix	457-461	5
α-helix	464-480	17

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Parathyroid hormone/parathyroid hormone-related peptide receptor	R	protein	478	Homo sapiens	Q03431 (AlphaFold model)
Long-acting parathyroid hormone analog	P	protein	36	Homo sapiens
Gs protein alpha subunit	A	protein	378	Bos taurus	P04896 (AlphaFold model), P63097 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	345	Rattus norvegicus	P54311 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	71	Bos taurus	P63212
Nanobody-35	N	protein	126	synthetic construct

Sequence of entity 1 (R), FASTA

>6NBI_1 Parathyroid hormone/parathyroid hormone-related peptide receptor (chains R)
DADDVMTKEEQIFLLHRAQAQCEKRLKEVLQRPASIMESDKGWTSASTSGKPRKDKASGK
LYPESEEDKEAPTGSRYRGRPCLPEWDHILCWPLGAPGEVVAVPCPDYIYDFNHKGHAYR
RCDRNGSWELVPGHNRTWANYSECVKFLTNETREREVFDRLAMIYTVGYSVSLASLTVAV
LILAYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGATLDEAERLTEEELRAIAQ
APPPPATAAAGYAGCRVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTV
FGWGLPAVFVAVWVSVRATLANTGCWDLSSGNKKWIIQVPILASIVLNFILFINIVRVLA
TKLRETNAGRCDTRQQYRKLLKSTLVLMPLFGVHYIVFMATPYTEVSGTLWQVQMHYEML
FNSFQGFFVAIIYCFCNGEVQAEIKKSWSRWTLALDFKRKARSGSSSYSYGPMVSHEF

Sequence of entity 2 (P), FASTA

>6NBI_2 Long-acting parathyroid hormone analog (chains P)
AVAEIQLMHQRAKWIQDARRRAFLHKLIAEIHTAEI

Sequence of entity 3 (A), FASTA

>6NBI_3 Gs protein alpha subunit (chains A)
MGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGAGESGKSTIVKQM
RILHVNGYSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGA
AEEGFMTAELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQD
VLRTRVKTTGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTAIIFVVASSSYNMV
IREDNQTNRLQEALNLFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFA
RYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCAVDTENIRRVF
NDCRDIIQRMHLRQYELL

Sequence of entity 4 (B), FASTA

>6NBI_4 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MGSLLQSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHL
AKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACG
GLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQ
QTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFF
PNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCN
VWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 5 (G), FASTA

>6NBI_5 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 6 (N), FASTA

>6NBI_6 Nanobody-35 (chains N)
QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASISY
TGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRGQ
GTQVTV

Ligands and cofactors

ID	Name	Formula	Copies
CLR	Cholesterol	C27 H46 O	3

Primary citation

Structure and dynamics of the active human parathyroid hormone receptor-1. Zhao, L.H., Ma, S., Sutkeviciute, I. et al. Science (2019) 364:148-153. DOI 10.1126/science.aav7942 · PubMed

Other PDB entries of the same protein (UniProt Q03431 (AlphaFold model), which also has an AlphaFold model), best resolution first:

5EMB 0.85 Å, Crystal structure of the SNX27 PDZ domain bound to the C-terminal phosphorylated PTHR…
4Z8J 0.95 Å, Crystal structure of the SNX27 PDZ domain bound to the C-terminal PTHR PDZ binding motif
7UZO 1.3 Å, Parathyroid hormone 1 receptor extracellular domain complexed with a peptide ligand…
3H3G 1.94 Å, Crystal structure of the extracellular domain of the human parathyroid hormone receptor…
3C4M 1.95 Å, Structure of human parathyroid hormone in complex with the extracellular domain of its…
8D51 2.0 Å, Parathyroid hormone 1 receptor extracellular domain complexed with a peptide ligand…
8D52 2.02 Å, Parathyroid hormone 1 receptor extracellular domain complexed with a peptide ligand…
7UZP 2.29 Å, parathyroid hormone 1 receptor extracellular domain complexed with a peptide ligand…
8BIA 2.4 Å, Crystal structure of Scribble PDZ1 with PTHR
6FJ3 2.5 Å, High resolution crystal structure of parathyroid hormone 1 receptor in complex with a…
8FLQ 2.55 Å, Human PTH1R in complex with PTH(1-34) and Gs
8JR9 2.57 Å, Small molecule agonist (PCO371) bound to human parathyroid hormone receptor type 1 (PTH1R)

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