9M54: Neuropeptide FF receptor 2 complex with NPVF

Cryo-EM structure of neuropeptide FF receptor 2 complex with NPVF. Determined by electron microscopy at 3.24 Å resolution. Released 23 Jul 2025.

Method: Electron microscopy
Resolution: 3.24 Å
Organisms: Homo sapiens, synthetic construct, Rattus norvegicus
Chains: 6
Atoms: 8,989
Mol. weight: 163.26 kDa
Released: 23 Jul 2025

Explore 9M54 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9M54 contains 41 α-helices and 71 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: 12 helices, 13 β-strands

Element	Residues	Length	Sheet
α-helix	7-31	25
β-strand	34-38	5	11
β-strand	39-40	2	12
α-helix	46-53	8
β-strand	185-189	5	11
β-strand	196-200	5	11
α-helix	208-210	3
α-helix	212-214	3
β-strand	220	1	11
β-strand	223-226	4	12
α-helix	227-230	4
β-strand	233	1	13
β-strand	241	1	13
α-helix	242-254	13
α-helix	262	1
β-strand	263	1	11
β-strand	264	1	14
β-strand	267-269	3	12
α-helix	271-280	10
α-helix	283-285	3
α-helix	296-309	14
β-strand	319	1	14
β-strand	322-323	2	12
α-helix	324-325	2
α-helix	331-351	21

Chain B: 4 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	2-25	24
α-helix	30-33	4
α-helix	34-36	3
α-helix	38-40	3
β-strand	45-51	7	4
β-strand	60-63	4	5
β-strand	69-73	5	5
β-strand	78-83	6	5
β-strand	89-94	6	5
β-strand	100-105	6	6
β-strand	111-116	6	6
β-strand	121-125	5	6
β-strand	134-139	6	6
β-strand	146-153	8	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	207-212	6	8
β-strand	218-222	5	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	304-308	5	10
β-strand	315-320	6	4
β-strand	327-331	5	4
β-strand	335-341	7	4

Chain G: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	9-22	14
α-helix	30-43	14
α-helix	53-55	3
α-helix	56-58	3

Chain L: 1 helix, 0 β-strands

Element	Residues	Length	Sheet
α-helix	4-7	4

Chain R: 17 helices, 6 β-strands

Element	Residues	Length	Sheet
β-strand	135-138	4	1
α-helix	147-172	26
α-helix	176-179	4
α-helix	182-195	14
α-helix	196-200	5
α-helix	201-209	9
α-helix	217-250	34
α-helix	259-275	17
α-helix	278-282	5
β-strand	287	1	2
β-strand	292-295	4	1
β-strand	296	1	3
β-strand	301	1	3
β-strand	307	1	2
α-helix	318-325	8
α-helix	326-331	6
α-helix	332-349	18
α-helix	372-388	17
α-helix	390-400	11
α-helix	403-405	3
α-helix	406-411	6
α-helix	412-416	5
α-helix	417-437	21

Chain S: 3 helices, 24 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	15
β-strand	10-12	3	16
β-strand	17-25	9	15
β-strand	33-39	7	16
β-strand	45-51	7	16
β-strand	58-60	3	16
α-helix	62-64	3
β-strand	68-73	6	15
α-helix	74-76	3
β-strand	78-84	7	15
α-helix	88-90	3
β-strand	92-99	8	16
β-strand	110-111	2	16
β-strand	115-119	5	16
β-strand	140-141	2	17
β-strand	146-148	3	18
β-strand	155-161	7	17
β-strand	166	1	19
β-strand	172	1	19
β-strand	174-179	6	18
β-strand	186-190	5	18
β-strand	194-195	2	18
β-strand	203-207	5	17
β-strand	211-216	6	17
β-strand	226-231	6	18
β-strand	239	1	18
β-strand	243-246	4	18

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Neuropeptide FF receptor 2	R	protein	420	Homo sapiens	Q9Y5X5 (AlphaFold model)
Neuropeptide VF	L	protein	9	synthetic construct
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	354	Rattus norvegicus	P54311 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	71	Bos taurus	P63212 (AlphaFold model)
Guanine nucleotide-binding protein G(i) subunit alpha-1	A	protein	354	Bos taurus	P63097 (AlphaFold model)
scfv16	S	protein	247	Mus musculus

Sequence of entity 1 (R), FASTA

>9M54_1 Neuropeptide FF receptor 2 (chains R)
MNEKWDTNSSENWHPIWNVNDTKHHLYSDINITYVNYYLHQPQVAAIFIISYFLIFFLCM
MGNTVVCFIVMRNKHMHTVTNLFILNLAISDLLVGIFCMPITLLDNIIAGWPFGNTMCKI
SGLVQGISVAASVFTLVAIAVDRFQCVVYPFKPKLTIKTAFVIIMIIWVLAITIMSPSAV
MLHVQEEKYYRVRLNSQNKTSPVYWCREDWPNQEMRKIYTTVLFANIYLAPLSLIVIMYG
RIGISLFRAAVPHTGRKNQEQWHVVSRKKQKIIKMLLIVALLFILSWLPLWTLMMLSDYA
DLSPNELQIINIYIYPFAHWLAFGNSSVNPIIYGFFNENFRRGFQEAFQLQLCQKRAKPM
EAYALKAKSHVLINTSNQLVQESTFQNPHGETLLYRKSAEKPQQELVMEELKETTNSSEI

Sequence of entity 2 (L), FASTA

>9M54_2 Neuropeptide VF (chains L)
VPNLPQRFX

Sequence of entity 3 (B), FASTA

>9M54_3 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MHHHHHHGSLLQSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRR
TLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSG
NYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALW
DIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDI
NAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGY
DDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWNGSS

Sequence of entity 4 (G), FASTA

>9M54_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 5 (A), FASTA

>9M54_5 Guanine nucleotide-binding protein G(i) subunit alpha-1 (chains A)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKSTIVKQMKIIHEAG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TTGIVETHFTFKDLHFKMFDVGAQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEM
NRMHESMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAA
AYIQCQFEDLNKRKDTKEIYTHFTCSTDTKNVQFVFDAVTDVIIKNNLKDCGLF

Sequence of entity 6 (S), FASTA

>9M54_6 scfv16 (chains S)
VQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYYA
DTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVSA
GGGGSGGGGSGGGGSADIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLEL

Primary citation

Structural basis of peptide recognition and modulation for neuropeptide FF receptors. Li, X., Zhang, H., Hu, W. et al. Cell Rep (2025) 44:116160-116160. DOI 10.1016/j.celrep.2025.116160 · 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…
9JFY 3.21 Å, Cryo-EM structure of Neuropeptide FF receptor 2 in complex with hNPSF and Gi

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