7TS0: Corticotropin releasing factor receptor 2

Cryo-EM structure of corticotropin releasing factor receptor 2 bound to Urocortin 1 and coupled with heterotrimeric Go protein. Determined by electron microscopy at 2.8 Å resolution. Released 9 Nov 2022.

Method: Electron microscopy
Resolution: 2.8 Å
Organisms: Homo sapiens, Rattus norvegicus, synthetic construct
Chains: 6
Atoms: 9,383
Mol. weight: 186.3 kDa
Released: 9 Nov 2022

Explore 7TS0 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7TS0 contains 39 α-helices and 66 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: 11 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	7-31	25
β-strand	34-40	7	3
α-helix	42-44	3
α-helix	46-54	9
α-helix	185	1
β-strand	186-191	6	3
β-strand	196-201	6	3
α-helix	211-217	7
β-strand	221-227	7	3
α-helix	229-231	3
β-strand	234	1	4
α-helix	235	1
β-strand	242	1	4
α-helix	243-255	13
β-strand	264-270	7	3
α-helix	272-281	10
α-helix	297-309	13
β-strand	320-323	4	3
α-helix	331-350	20

Chain B: 3 helices, 29 β-strands

Element	Residues	Length	Sheet
α-helix	4-25	22
α-helix	32-34	3
α-helix	38-39	2
β-strand	45-51	7	5
β-strand	58-63	6	6
β-strand	69-74	6	6
β-strand	78-83	6	6
β-strand	88-94	7	6
β-strand	100-105	6	7
β-strand	111-116	6	7
β-strand	121-125	5	7
β-strand	134-139	6	7
β-strand	146-151	6	8
β-strand	156-161	6	8
β-strand	166-170	5	8
β-strand	175-180	6	8
β-strand	189-192	4	9
β-strand	198-202	5	9
β-strand	208-212	5	9
β-strand	218-222	5	9
β-strand	229-234	6	10
β-strand	240-245	6	10
β-strand	250-254	5	10
β-strand	259-264	6	10
β-strand	273-278	6	11
β-strand	284-289	6	11
β-strand	294-298	5	11
β-strand	304-308	5	11
β-strand	315-320	6	5
β-strand	327-331	5	5
β-strand	335-341	7	5
β-strand	342	1	12

Chain G: 2 helices, 1 β-strand

Element	Residues	Length	Sheet
α-helix	7-23	17
α-helix	30-43	14
β-strand	54	1	12

Chain H: 6 helices, 24 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	13
β-strand	10-12	3	14
β-strand	18-25	8	13
α-helix	29-31	3
β-strand	33-39	7	14
β-strand	45-51	7	14
β-strand	58-60	3	14
β-strand	68-73	6	13
β-strand	78-83	6	13
α-helix	88-90	3
β-strand	92-99	8	14
β-strand	110-111	2	14
β-strand	115-119	5	14
α-helix	138-139	2
β-strand	140-141	2	15
β-strand	146-148	3	16
β-strand	155-161	7	15
β-strand	166	1	17
β-strand	172	1	17
β-strand	174-179	6	16
β-strand	185-190	6	16
β-strand	194-195	2	16
α-helix	196	1
β-strand	203-207	5	15
β-strand	211-216	6	15
α-helix	221-223	3
β-strand	226-231	6	16
α-helix	237	1
β-strand	239	1	16
β-strand	243-246	4	16

Chain P: 16 helices, 3 β-strands

Element	Residues	Length	Sheet
β-strand	67-68	2	1
β-strand	71-72	2	1
α-helix	99-101	3
α-helix	103-105	3
α-helix	111-137	27
α-helix	147-170	24
α-helix	174-178	5
α-helix	182-213	32
α-helix	220-228	9
α-helix	229-233	5
α-helix	235-249	15
α-helix	253-255	3
α-helix	266-297	32
α-helix	301-319	19
α-helix	322-325	4
β-strand	328	1	2
α-helix	335-355	21
α-helix	356-361	6
α-helix	364-382	19

Chain U: 1 helix, 1 β-strand

Element	Residues	Length	Sheet
β-strand	5	1	2
α-helix	9-36	28

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Corticotropin-releasing factor receptor 2,Corticotropin-releasing factor receptor…	P	protein	560	Homo sapiens	Q13324 (AlphaFold model)
Urocortin	U	protein	40	Homo sapiens	P55089 (AlphaFold model)
Dominant negative Go alpha subunit	A	protein	353	Homo sapiens
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	400	Rattus norvegicus	P54311 (AlphaFold model)
G protein gamma subunit	G	protein	71	Rattus norvegicus	A0A9X9ZA26 (AlphaFold model)
scFV16	H	protein	247	synthetic construct

Sequence of entity 1 (P), FASTA

>7TS0_1 Corticotropin-releasing factor receptor 2,Corticotropin-releasing factor receptor 2,Corticotropin-releasing factor receptor 2,Corticotropin-releasing factor receptor 2,Human corticotropin releasing factor receptor 2 (chains P)
DAALLHSLLEANCSLALAEELLLDGWGPPLDPEGPYSYCNTTLDQIGTCWPRSAAGALVE
RPCPEYFNGVKYNTTRNAYRECLENGTWASKINYSQCEPILDDKQRKYDLHYRIALVVNY
LGHCVSVAALVAAFLLFLALRSIRCLRNVIHWNLITTFILRNVMWFLLQLVDHEVHESNE
VWCRCITTIFNYFVVTNFFWMFVEGCYLHTAIVMTYSTERLRKCLFLFIGWCIPFPIIVA
WAIGKLYYENEQCWFGKEPGDLVDYIYQGPIILVLLINFVFLFNIVRILMTKLRASTTSE
TIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDLSQIMFIYFNSFLQSFQGFFVSVFYCF
FNGEVRSAVRKRWHRWQDHHSLRVPMAGSSGGGGSGGGGSSGVFTLEDFVGDWEQTAAYN
LDQVLEQGGVSSLLQNLAVSVTPIQRIVRSGENALKIDIHVIIPYEGLSADQMAQIEEVF
KVVYPVDDHHFKVILPYGTLVIDGVTPNMLNYFGRPYEGIAVFDGKKITVTGTLWNGNKI
IDERLITPDGSMLFRVTINS

Sequence of entity 2 (U), FASTA

>7TS0_2 Urocortin (chains U)
DNPSLSIDLTFHLLRTLLELARTQSQRERAEQNRIIFDSV

Sequence of entity 3 (A), FASTA

>7TS0_3 Dominant negative Go alpha subunit (chains A)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAKDVKLLLLGAGESGKSTIVKQMKIIHEAG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TTGIVETHFTFKNLHFRLFDVGAQRDERRKWIHCFEDVTAIIFCVALSGYDQVLHEDETT
NRMQESLNLFKSICNNKFFIDTSIILFLNKKDLFGEKIKKSPLTICFPEYTGPNTYEDAA
AYIQAQFESKNRSPNKEIYCHMTCSTDTNNIQVVFDAVTDIIIANNLRGCGLY

Sequence of entity 4 (B), FASTA

>7TS0_4 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 5 (G), FASTA

>7TS0_5 G protein gamma subunit (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 6 (H), FASTA

>7TS0_6 scFV16 (chains H)
VQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYYA
DTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVSA
GGGGSGGGGSGGGGSADIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLEL

Primary citation

Structure insights into selective coupling of G protein subtypes by a class B G protein-coupled receptor. Zhao, L.H., Lin, J., Ji, S.Y. et al. Nat Commun (2022) 13:6670-6670. DOI 10.1038/s41467-022-33851-3 · 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
6PB1 2.8 Å, Cryo-EM structure of Urocortin 1-bound Corticotropin-releasing factor 2 receptor in…
7TRY 3.7 Å, Cryo-EM structure of corticotropin releasing factor receptor 2 bound to Urocortin 1 and…

Browse structure collections

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