6PB0: Corticotropin-releasing factor receptor 1

Cryo-EM structure of Urocortin 1-bound Corticotropin-releasing factor 1 receptor in complex with Gs protein and Nb35. Determined by electron microscopy at 3.0 Å resolution. Released 12 Feb 2020.

Method: Electron microscopy
Resolution: 3.0 Å
Organisms: Homo sapiens, synthetic construct
Chains: 6
Atoms: 8,827
Mol. weight: 156.96 kDa
Ligands: CLR, PLM
Released: 12 Feb 2020

Explore 6PB0 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

6PB0 contains 35 α-helices and 46 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: 10 helices, 7 β-strands

Element	Residues	Length	Sheet
α-helix	12-37	26
β-strand	41-47	7	1
α-helix	53-59	7
β-strand	207-213	7	1
β-strand	218-224	7	1
α-helix	235-237	3
β-strand	243-248	6	1
α-helix	266-277	12
β-strand	286-291	6	1
α-helix	295-300	6
α-helix	308-311	4
α-helix	319-321	3
α-helix	325-327	3
α-helix	332-349	18
β-strand	359-360	2	1
β-strand	363	1	1
α-helix	371-390	20

Chain B: 4 helices, 29 β-strands

Element	Residues	Length	Sheet
α-helix	4-24	21
α-helix	30-33	4
α-helix	38-39	2
β-strand	43	1	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	89-94	6	4
α-helix	95	1
β-strand	100-105	6	5
β-strand	111-116	6	5
β-strand	121-125	5	5
β-strand	135-139	5	5
β-strand	146-151	6	6
β-strand	156-161	6	6
β-strand	166-170	5	6
β-strand	176-180	5	6
β-strand	189-192	4	7
β-strand	198-202	5	7
β-strand	208-212	5	7
β-strand	218-222	5	7
β-strand	229-234	6	8
β-strand	240-245	6	8
β-strand	250-254	5	8
β-strand	260-264	5	8
β-strand	275-278	4	2
β-strand	284-288	5	2
β-strand	294-298	5	2
β-strand	304-308	5	2
β-strand	315-320	6	3
β-strand	327-331	5	3
β-strand	336-339	4	3

Chain G: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	9-23	15
α-helix	27-29	3
α-helix	30-43	14
α-helix	53-54	2

Chain N: 2 helices, 10 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	9
β-strand	18-25	8	9
α-helix	29-31	3
β-strand	34-39	6	10
β-strand	45-51	7	10
β-strand	58-60	3	10
α-helix	62-64	3
β-strand	68-73	6	9
β-strand	78-83	6	9
β-strand	92-98	7	10
β-strand	118	1	10
β-strand	122-124	3	10

Chain R: 14 helices, 0 β-strands

Element	Residues	Length
α-helix	113-143	31
α-helix	150-174	25
α-helix	178-182	5
α-helix	186-217	32
α-helix	220-222	3
α-helix	228-232	5
α-helix	233-237	5
α-helix	239-252	14
α-helix	257-259	3
α-helix	270-301	32
α-helix	305-323	19
α-helix	340-360	21
α-helix	361-365	5
α-helix	368-385	18

Chain U: 1 helix, 0 β-strands

Element	Residues	Length	Sheet
α-helix	9-39	31

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Corticotropin-releasing factor receptor 1	R	protein	375	Homo sapiens	P34998 (AlphaFold model)
Urocortin	U	protein	40	Homo sapiens	P55089 (AlphaFold model)
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short,Guanine nucleotide-binding…	A	protein	378	Homo sapiens	P63092 (AlphaFold model), P63096 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	345	Homo sapiens	P62873
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	71	Homo sapiens	P59768
Nanobody 35	N	protein	140	synthetic construct

Sequence of entity 1 (R), FASTA

>6PB0_1 Corticotropin-releasing factor receptor 1 (chains R)
SLQDQHCESLSLASNISGLQCNASVDLIGTCWPRSPAGQLVVRPCPAFFYGVRYNTTNNG
YRECLANGSWAARVNYSECQEILNEEKKSKVHYHVAVIINYLGHCISLVALLVAFVLFLR
LRSIRCLRNIIHWNLISAFILRNATWFVVQLTMSPEVHQSNVGWCRLVTAAYNYFHVTNF
FWMFGEGCYLHTAIVLTYSTDRLRKWMFICIGWGVPFPIIVAWAIGKLYYDNEKCWFGKR
PGVYTDYIYQGPMILVLLINFIFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLL
GITYMLFFVNPGEDEVSRVVFIYFNSFLESFQGFFVSVFYCFLNSEVRSAIRKRWHRWQD
KHSIRARVARAMSIP

Sequence of entity 2 (U), FASTA

>6PB0_2 Urocortin (chains U)
DNPSLSIDLTFHLLRTLLELARTQSQRERAEQNRIIFDSV

Sequence of entity 3 (A), FASTA

>6PB0_3 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short,Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains A)
MGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGAGESGKSTIVKQM
RILHVNGYSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGA
AEEGFMTAELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQD
VLRTRVKTTGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFNDVTAIIFVVASSSYNMV
IREDNQTNRLQEALNLFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFA
RYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCSVDTENIRRVF
NDCRDIIQRMHLRQYELL

Sequence of entity 4 (B), FASTA

>6PB0_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

>6PB0_5 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 6 (N), FASTA

>6PB0_6 Nanobody 35 (chains N)
MAQVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASI
SYTGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYR
GQGTQVTVSSHHHHHHEPEA

Ligands and cofactors

ID	Name	Formula	Copies
CLR	Cholesterol	C27 H46 O	5
PLM	Palmitic acid	C16 H32 O2	7

Primary citation

Molecular Basis for Hormone Recognition and Activation of Corticotropin-Releasing Factor Receptors. Ma, S., Shen, Q., Zhao, L.H. et al. Mol Cell (2020) 77:669. DOI 10.1016/j.molcel.2020.01.013 · PubMed

Other PDB entries of the same protein (UniProt P34998 (AlphaFold model), which also has an AlphaFold model), best resolution first:

3EHU 1.96 Å, Crystal structure of the extracellular domain of human corticotropin releasing factor…
8GTI 2.2 Å, Corticotropin-releasing hormone receptor 1(CRF1R) bound with BMK-C205 by XFEL
8GTM 2.6 Å, Corticotropin-releasing hormone receptor 1(CRF1R) bound with BMK-C203 by XFEL
8GTG 2.75 Å, Corticotropin-releasing hormone receptor 1(CRF1R) bound with BMK-I-152 by XFEL
3EHS 2.76 Å, Crystal structure of the extracellular domain of human corticotropin releasing factor…
6P9X 2.91 Å, CRF1 Receptor Gs GPCR protein complex with CRF1 peptide
4K5Y 2.98 Å, Crystal structure of human corticotropin-releasing factor receptor 1 (CRF1R) in complex…
4Z9G 3.18 Å, Crystal structure of human corticotropin-releasing factor receptor 1 (CRF1R) in complex…
3EHT 3.4 Å, Crystal structure of the extracellular domain of human corticotropin releasing factor…
2L27 NMR Structure of the ECD1 of CRF-R1 in complex with a peptide agonist

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