9JFY: Neuropeptide FF receptor 2

Cryo-EM structure of Neuropeptide FF receptor 2 in complex with hNPSF and Gi. Determined by electron microscopy at 3.21 Å resolution. Released 9 Apr 2025.

Method: Electron microscopy
Resolution: 3.21 Å
Organisms: Homo sapiens, Mus musculus
Chains: 6
Atoms: 8,805
Mol. weight: 164.87 kDa
Released: 9 Apr 2025

Explore 9JFY in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9JFY contains 32 α-helices and 64 β-strands across 5 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	7-31	25
β-strand	34-39	6	3
β-strand	185-190	6	3
β-strand	195-200	6	3
α-helix	208-210	3
α-helix	212-215	4
β-strand	220-226	7	3
α-helix	227-230	4
α-helix	242-254	13
β-strand	263-269	7	3
α-helix	271-277	7
α-helix	296-308	13
β-strand	319-323	5	3
α-helix	328-350	23

Chain B: 2 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	7-25	19
α-helix	30-33	4
β-strand	47-51	5	4
β-strand	58-63	6	5
β-strand	69-74	6	5
β-strand	78-83	6	5
β-strand	88-94	7	5
β-strand	100-105	6	6
β-strand	111-116	6	6
β-strand	120-125	6	6
β-strand	134-140	7	6
β-strand	146-151	6	7
β-strand	156-161	6	7
β-strand	165-170	6	7
β-strand	176-181	6	7
β-strand	187-192	6	8
β-strand	198-203	6	8
β-strand	208-212	5	8
β-strand	217-222	6	8
β-strand	229-234	6	9
β-strand	240-245	6	9
β-strand	250-254	5	9
β-strand	259-264	6	9
β-strand	273-278	6	10
β-strand	284-289	6	10
β-strand	294-298	5	10
β-strand	303-308	6	10
β-strand	315-320	6	4
β-strand	327-331	5	4
β-strand	336-339	4	4

Chain G: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	10-23	14
α-helix	30-43	14
α-helix	53-55	3

Chain R: 14 helices, 5 β-strands

Element	Residues	Length	Sheet
β-strand	33-35	3	1
β-strand	38	1	2
α-helix	42-72	31
α-helix	79-97	19
α-helix	99-107	9
β-strand	108	1	2
α-helix	115-148	34
α-helix	153-156	4
α-helix	157-181	25
β-strand	182-193	12	1
β-strand	200-208	9	1
α-helix	213-224	12
α-helix	225-229	5
α-helix	230-247	18
α-helix	267-299	33
α-helix	304-309	6
α-helix	310-314	5
α-helix	315-335	21
α-helix	338-341	4

Chain S: 5 helices, 25 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	11
β-strand	11-12	2	12
β-strand	17-25	9	11
α-helix	29-31	3
β-strand	33-39	7	13
β-strand	45-51	7	13
α-helix	53-55	3
β-strand	58-60	3	13
β-strand	68-73	6	11
β-strand	78-84	7	11
α-helix	88-90	3
β-strand	92-99	8	13
β-strand	110-111	2	13
β-strand	115-117	3	13
β-strand	118-119	2	12
β-strand	140-142	3	14
β-strand	146-147	2	15
β-strand	155-161	7	14
β-strand	166	1	16
β-strand	172	1	16
β-strand	174-179	6	15
β-strand	186-190	5	15
β-strand	194-195	2	15
α-helix	196	1
β-strand	204-208	5	14
β-strand	211-216	6	14
α-helix	221-223	3
β-strand	226-231	6	15
β-strand	239	1	15
β-strand	243-245	3	15

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Isoform 2 of Neuropeptide FF receptor 2	R	protein	429	Homo sapiens	Q9Y5X5 (AlphaFold model)
Neuropeptide SF	L	protein	12	Homo sapiens	O15130 (AlphaFold model)
Guanine nucleotide-binding protein G(i) subunit alpha-1	A	protein	354	Homo sapiens	P63096 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	345	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	71	Homo sapiens	P59768
single-chain antibody Fv fragment (scFv16)	S	protein	259	Mus musculus

Sequence of entity 1 (R), FASTA

>9JFY_1 Isoform 2 of Neuropeptide FF receptor 2 (chains R)
DYKDDDDASSENWHPIWNVNDTKHHLYSDINITYVNYYLHQPQVAAIFIISYFLIFFLCM
MGNTVVCFIVMRNKHMHTVTNLFILNLAISDLLVGIFCMPITLLDNIIAGWPFGNTMCKI
SGLVQGISVAASVFTLVAIAVDRFQCVVYPFKPKLTIKTAFVIIMIIWVLAITIMSPSAV
MLHVQEEKYYRVRLNSQNKTSPVYWCREDWPNQEMRKIYTTVLFANIYLAPLSLIVIMYG
RIGISLFRAAVPHTGRKNQEQWHVVSRKKQKIIKMLLIVALLFILSWLPLWTLMMLSDYA
DLSPNELQIINIYIYPFAHWLAFGNSSVNPIIYGFFNENFRRGFQEAFQLQLCQKRAKPM
EAYALKAKSHVLINTSNQLVQESTFQNPHGETLLYRKSAEKPQQELVMEELKETTNSSEI
HMGLEVLFQ

Sequence of entity 2 (L), FASTA

>9JFY_2 Neuropeptide SF (chains L)
SQAFLFQPQRFX

Sequence of entity 3 (A), FASTA

>9JFY_3 Guanine nucleotide-binding protein G(i) subunit alpha-1 (chains A)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKSTIVKQMKIIHEAG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TTGIVETHFTFKDLHFKMFDVGGQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEM
NRMHESMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAA
AYIQCQFEDLNKRKDTKEIYTHFTCATDTKNVQFVFDAVTDVIIKNNLKDCGLF

Sequence of entity 4 (B), FASTA

>9JFY_4 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
GPGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHL
AKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACG
GLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQ
QTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFF
PNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCN
VWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 5 (G), FASTA

>9JFY_5 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 6 (S), FASTA

>9JFY_6 single-chain antibody Fv fragment (scFv16) (chains S)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELKAAAHHHHHHHH

Primary citation

Structural insights into the selective recognition of RF-amide peptides by neuropeptide FF receptor 2. Kim, J., Hong, S., Lee, H. et al. EMBO Rep (2025) 26:2413-2434. DOI 10.1038/s44319-025-00428-2 · PubMed

Other PDB entries of the same protein (UniProt Q9Y5X5 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9M1O 2.49 Å, Cryo-EM structures of NPFFR2 complex with neuropeptide FF
9V1H 2.85 Å, Cryo-EM structure of Gi-coupled NPFF2R in complex with GUB08248
9JG0 2.91 Å, Cryo-EM structure of neuropeptide FF receptor 2 in the ligand-free state with BRIL…
9M54 3.24 Å, Cryo-EM structure of neuropeptide FF receptor 2 complex with NPVF

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