9M1O: NPFFR2 complex with neuropeptide FF

Cryo-EM structures of NPFFR2 complex with neuropeptide FF. Determined by electron microscopy at 2.49 Å resolution. Released 23 Jul 2025.

Method: Electron microscopy
Resolution: 2.49 Å
Organisms: Escherichia coli, Homo sapiens, Rattus norvegicus
Chains: 6
Atoms: 9,085
Mol. weight: 183.01 kDa
Released: 23 Jul 2025

Explore 9M1O in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9M1O contains 36 α-helices and 62 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: 11 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	7-31	25
β-strand	34-40	7	14
α-helix	46-52	7
β-strand	185-189	5	14
β-strand	196-200	5	14
α-helix	208-210	3
α-helix	212-215	4
β-strand	220-226	7	14
α-helix	227-230	4
β-strand	233	1	15
β-strand	241	1	15
α-helix	242-254	13
β-strand	263-269	7	14
α-helix	271-277	7
α-helix	283-285	3
α-helix	296-309	14
β-strand	319-323	5	14
α-helix	324-325	2
α-helix	331-351	21

Chain B: 5 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	46-51	6	2
β-strand	60-63	4	3
β-strand	69-73	5	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	120-125	6	4
β-strand	134-140	7	4
β-strand	146-153	8	5
β-strand	156-161	6	5
β-strand	165-170	6	5
β-strand	175-181	7	5
β-strand	187-192	6	6
β-strand	198-203	6	6
β-strand	208-212	5	6
β-strand	217-222	6	6
β-strand	229-234	6	7
β-strand	240-245	6	7
β-strand	250-254	5	7
β-strand	259-264	6	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	336-340	5	2

Chain G: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	9-23	15
α-helix	30-43	14
α-helix	53-55	3

Chain R: 12 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	144-174	31
α-helix	181-209	29
α-helix	217-250	34
α-helix	255-258	4
α-helix	259-276	18
α-helix	278-282	5
β-strand	288-293	6	1
β-strand	304-306	3	1
α-helix	315-326	12
α-helix	327-331	5
α-helix	332-349	18
α-helix	369-400	32
α-helix	406-437	32
α-helix	440-442	3

Chain S: 5 helices, 24 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	9
β-strand	10-12	3	10
β-strand	17-25	9	9
α-helix	29-31	3
β-strand	33-39	7	10
β-strand	45-51	7	10
β-strand	58-60	3	10
β-strand	68-73	6	9
α-helix	74-76	3
β-strand	78-84	7	9
α-helix	88-90	3
β-strand	92-99	8	10
β-strand	110-111	2	10
β-strand	115-119	5	10
α-helix	138-139	2
β-strand	140-141	2	11
β-strand	146-148	3	12
β-strand	155-161	7	11
β-strand	166	1	13
β-strand	172	1	13
β-strand	174-179	6	12
β-strand	186-190	5	12
β-strand	194-195	2	12
α-helix	196	1
β-strand	203-207	5	11
β-strand	211-216	6	11
β-strand	225-231	7	12
β-strand	239	1	12
β-strand	243-246	4	12

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Soluble cytochrome b562,Neuropeptide FF receptor 2,Neuropeptide FF receptor 2	R	protein	589	Escherichia coli, Homo sapiens	Q9Y5X5 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	366	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)
Morphine-modulating neuropeptide B	L	protein	9	synthetic construct	P15507
scfv16	S	protein	247	synthetic construct
Guanine nucleotide-binding protein G(i) subunit alpha-1	A	protein	354	Homo sapiens	P63096

Sequence of entity 1 (R), FASTA

>9M1O_1 Soluble cytochrome b562,Neuropeptide FF receptor 2,Neuropeptide FF receptor 2 (chains R)
MDSKGSSQKGSRLLLLLVVSNLLLCQGVVSDYKDDDDVDGSAENLYFQGASADLEDNWET
LNDNLKVIEKADNAAQVKDALTKMRAAALDAQKATPPKLEDKSPDSPEMKDFRHGFDILV
GQIDDALKLANEGKVKEAQAAAEQLKTTRNAYIQKYLMNEKWDTNSSENWHPIWNVNDTK
HHLYSDINITYVNYYLHQPQVAAIFIISYFLIFFLCMMGNTVVCFIVMRNKHMHTVTNLF
ILNLAISDLLVGIFCMPITLLDNIIAGWPFGNTMCKISGLVQGISVAASVFTLVAIAVDR
FQCVVYPFKPKLTIKTAFVIIMIIWVLAITIMSPSAVMLHVQEEKYYRVRLNSQNKTSPV
YWCREDWPNQEMRKIYTTVLFANIYLAPLSLIVIMYGRIGISLFRAAVPHTGRKNQEQWH
VVSRKKQKIIKMLLIVALLFILSWLPLWTLMMLSDYADLSPNELQIINIYIYPFAHWLAF
GNSSVNPIIYGFFNENFRRGFQEAFQLQLCQKRAKPMEAYALKAKSHVLINTSNQLVQES
TFQNPHGETLLYRKSAEKPQQELVMEELKETTNSSEIHHHHHHHHHHHH

Sequence of entity 2 (B), FASTA

>9M1O_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MHHHHHHGSLLQSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRR
TLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSG
NYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALW
DIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDI
NAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGY
DDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWNGSSGGGGSG
GGGSSG

Sequence of entity 3 (G), FASTA

>9M1O_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (L), FASTA

>9M1O_4 Morphine-modulating neuropeptide B (chains L)
FLFQPQRFX

Sequence of entity 5 (S), FASTA

>9M1O_5 scfv16 (chains S)
VQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYYA
DTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVSA
GGGGSGGGGSGGGGSADIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLEL

Sequence of entity 6 (A), FASTA

>9M1O_6 Guanine nucleotide-binding protein G(i) subunit alpha-1 (chains A)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAREVKLLLLGAGESGKSTIVKQMKIIHEAG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TTGIVETHFTFKDLHFKMFDVGAQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEM
NRMHESMKLFDSICNNKWFTDTSIILFLNKKDLFEEKIKKSPLTICYPEYAGSNTYEEAA
AYIQCQFEDLNKRKDTKEIYTHFTCSTDTKNVQFVFDAVTDVIIKNNLKDCGLF

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:

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
9M54 3.24 Å, Cryo-EM structure of neuropeptide FF receptor 2 complex with NPVF

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