6PB1: Corticotropin-releasing factor receptor 2

Cryo-EM structure of Urocortin 1-bound Corticotropin-releasing factor 2 receptor in complex with Gs protein and Nb35. Determined by electron microscopy at 2.8 Å resolution. Released 12 Feb 2020.

Method: Electron microscopy
Resolution: 2.8 Å
Organisms: Homo sapiens, synthetic construct
Chains: 6
Atoms: 8,785
Mol. weight: 157.67 kDa
Ligands: PLM, CLR
Released: 12 Feb 2020

Explore 6PB1 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

6PB1 contains 34 α-helices and 45 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: 9 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	12-37	26
β-strand	41-47	7	1
α-helix	53-59	7
β-strand	207-214	8	1
β-strand	217-224	8	1
β-strand	243-249	7	1
α-helix	265-277	13
β-strand	286-292	7	1
α-helix	294-300	7
α-helix	308-311	4
α-helix	313-315	3
α-helix	326-327	2
α-helix	332-349	18
β-strand	359-363	5	1
α-helix	371-390	20

Chain B: 4 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	4-25	22
α-helix	30-33	4
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
α-helix	95	1
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	166-170	5	5
β-strand	175-180	6	5
β-strand	189-192	4	6
β-strand	198-202	5	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	294-298	5	8
β-strand	304-308	5	8
β-strand	315-320	6	2
β-strand	327-331	5	2
β-strand	336-339	4	2

Chain G: 2 helices, 0 β-strands

Element	Residues	Length	Sheet
α-helix	8-23	16
α-helix	30-43	14

Chain N: 2 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	9
β-strand	10-11	2	10
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
β-strand	68-73	6	9
β-strand	78-83	6	9
α-helix	88-90	3
β-strand	92-98	7	10
β-strand	118	1	10
β-strand	122-125	4	10

Chain P: 16 helices, 0 β-strands

Element	Residues	Length
α-helix	111-140	30
α-helix	147-170	24
α-helix	174-178	5
α-helix	182-213	32
α-helix	219-221	3
α-helix	224-228	5
α-helix	229-233	5
α-helix	237-247	11
α-helix	253-255	3
α-helix	266-297	32
α-helix	301-319	19
α-helix	321-324	4
α-helix	334-349	16
α-helix	351-356	6
α-helix	357-361	5
α-helix	364-381	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 2	P	protein	387	Homo sapiens	Q13324 (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 (P), FASTA

>6PB1_1 Corticotropin-releasing factor receptor 2 (chains P)
DAALLHSLLEANCSLALAEELLLDGWGPPLDPEGPYSYCNTTLDQIGTCWPRSAAGALVE
RPCPEYFNGVKYNTTRNAYRECLENGTWASKINYSQCEPILDDKQRKYDLHYRIALVVNY
LGHCVSVAALVAAFLLFLALRSIRCLRNVIHWNLITTFILRNVMWFLLQLVDHEVHESNE
VWCRCITTIFNYFVVTNFFWMFVEGCYLHTAIVMTYSTERLRKCLFLFIGWCIPFPIIVA
WAIGKLYYENEQCWFGKEPGDLVDYIYQGPIILVLLINFVFLFNIVRILMTKLRASTTSE
TIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDLSQIMFIYFNSFLQSFQGFFVSVFYCF
FNGEVRSAVRKRWHRWQDHHSLRVPMA

Sequence of entity 2 (U), FASTA

>6PB1_2 Urocortin (chains U)
DNPSLSIDLTFHLLRTLLELARTQSQRERAEQNRIIFDSV

Sequence of entity 3 (A), FASTA

>6PB1_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

>6PB1_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

>6PB1_5 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 6 (N), FASTA

>6PB1_6 Nanobody 35 (chains N)
MAQVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASI
SYTGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYR
GQGTQVTVSSHHHHHHEPEA

Ligands and cofactors

ID	Name	Formula	Copies
PLM	Palmitic acid	C16 H32 O2	5
CLR	Cholesterol	C27 H46 O	4

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 Q13324 (AlphaFold model), which also has an AlphaFold model), best resolution first:

3N93 2.5 Å, Crystal structure of human CRFR2 alpha extracellular domain in complex with Urocortin 3
3N95 2.72 Å, Crystal structure of human CRFR2 alpha extracellular domain in complex with Urocortin 2
3N96 2.75 Å, Crystal structure of human CRFR2 alpha extracellular domain in complex with Urocortin 1
7TS0 2.8 Å, Cryo-EM structure of corticotropin releasing factor receptor 2 bound to Urocortin 1 and…
7TRY 3.7 Å, Cryo-EM structure of corticotropin releasing factor receptor 2 bound to Urocortin 1 and…

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