8FMZ: Neurotensin receptor allosterism revealed

Neurotensin receptor allosterism revealed in complex with a biased allosteric modulator. Determined by electron microscopy at 2.59 Å resolution. Released 29 Mar 2023.

Method: Electron microscopy
Resolution: 2.59 Å
Organisms: Escherichia coli, Homo sapiens, Lama glama
Chains: 6
Atoms: 8,768
Mol. weight: 150.28 kDa
Released: 29 Mar 2023

Explore 8FMZ in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8FMZ contains 40 α-helices and 61 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: 15 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	53-55	3
α-helix	64-89	26
α-helix	102-124	23
α-helix	125-130	6
α-helix	138-172	35
α-helix	174-180	7
α-helix	183-200	18
α-helix	202-205	4
β-strand	208-212	5	14
α-helix	220-222	3
β-strand	223-227	5	14
α-helix	231-242	12
α-helix	243-247	5
α-helix	248-265	18
α-helix	304-333	30
α-helix	341-366	26
α-helix	367-371	5

Chain B: 10 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	7-30	24
β-strand	33-40	8	1
α-helix	46-48	3
β-strand	69-76	8	1
β-strand	79-86	8	1
α-helix	95-100	6
β-strand	105-111	7	1
α-helix	118-129	12
α-helix	132-134	3
β-strand	138-144	7	1
α-helix	146-155	10
α-helix	160-162	3
α-helix	165-169	5
α-helix	184-203	20
β-strand	211-215	5	1
α-helix	223-242	20

Chain C: 5 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	4-24	21
α-helix	30-32	3
α-helix	34-36	3
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
β-strand	100-105	6	4
β-strand	111-116	6	4
β-strand	121-125	5	4
α-helix	129-131	3
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	187-192	6	6
β-strand	198-203	6	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	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	336-339	4	2

Chain D: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	12-23	12
α-helix	30-43	14
α-helix	45-47	3
α-helix	53-55	3

Chain E: 6 helices, 25 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
α-helix	53-55	3
β-strand	58-60	3	10
β-strand	68-73	6	9
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	113	1	9
β-strand	115-119	5	10
α-helix	125-127	3
β-strand	128-130	3	11
β-strand	134-136	3	12
β-strand	143-149	7	11
β-strand	154	1	13
β-strand	160	1	13
β-strand	162-167	6	12
β-strand	174-178	5	12
β-strand	182-183	2	12
α-helix	184	1
β-strand	191-196	6	11
β-strand	199-204	6	11
β-strand	214-219	6	12
α-helix	225	1
β-strand	227	1	12
β-strand	231-234	4	12

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
MiniGq	B	protein	246	Escherichia coli
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	C	protein	358	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	D	protein	71	Homo sapiens	P59768 (AlphaFold model)
scFv16	E	protein	267	Lama glama
Neurotensin receptor type 1	A	protein	405	Rattus norvegicus	P20789 (AlphaFold model)
Neurotensin/neuromedin N	F	protein	6	Rattus norvegicus	P20068 (AlphaFold model)

Sequence of entity 1 (B), FASTA

>8FMZ_1 MiniGq (chains B)
MGSTVSAEDKAAAERSKMIDKNLREDGEKARRTLRLLLLGADNSGKSTIVKQMRILHGGS
GGSGGTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTAIIFVVDSSDYNRLQE
ALNDFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEP
GEDPRVTRAKYFIRKEFVDISTASGDGRHICYPHFTCAVDTENARRIFNDCKDIILQMNL
REYNLV

Sequence of entity 2 (C), FASTA

>8FMZ_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains C)
MHHHHHHLEVLFQGPGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGR
IQMRTRRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMT
CAYAPSGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSG
DTTCALWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTF
TGHESDINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSG
RLLLAGYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (D), FASTA

>8FMZ_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains D)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (E), FASTA

>8FMZ_4 scFv16 (chains E)
DVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYY
ADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVS
SGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQR
PGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFG
AGTKLELKAAALEVLFQGPHHHHHHHH

Sequence of entity 5 (A), FASTA

>8FMZ_5 Neurotensin receptor type 1 (chains A)
MHHHHHHHHHHSDLEVLFQGPLGSGAPTSESDTAGPNSDLDVNTDIYSKVLVTAIYLALF
VVGTVGNSVTLFTLARKKSLQSLQSTVHYHLGSLALSDLLILLLAMPVELYNFIWVHHPW
AFGDAGCRGYYFLRDACTYATALNVASLSVERYLAICHPFKAKTLMSRSRTKKFISAIWL
ASALLAIPMLFTMGLQNRSADGTHPGGLVCTPIVDTATVKVVIQVNTFMSFLFPMLVISI
LNTVIANKLTVMVHQAAEQGRVCTVGTHNGLEHSTFNMTIEPGRVQALRHGVLVLRAVVI
AFVVCWLPYHVRRLMFCYISDEQWTTFLFDFYHYFYMLTNALFYASSAINPILYNLVSAN
FRQVFLSTLACLCPGWRHRRKKRPTFSRKPNSMSSNHAFSTSATR

Sequence of entity 6 (F), FASTA

>8FMZ_6 Neurotensin/neuromedin N (chains F)
RRPYIL

Primary citation

Neurotensin Receptor Allosterism Revealed in Complex with a Biased Allosteric Modulator. Krumm, B.E., DiBerto, J.F., Olsen, R.H.J. et al. Biochemistry (2023) 62:1233-1248. DOI 10.1021/acs.biochem.3c00029 · PubMed

Other PDB entries of the same protein (UniProt P62873 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8QEH 1.43 Å, Crystal structure of the G11 protein heterotrimer bound to FR900359 inhibitor
8QEG 1.7 Å, Crystal structure of the G11 protein heterotrimer bound to YM-254890 inhibitor
8F0K 1.9 Å, Human Amylin3 Receptor in complex with Gs and Pramlintide analogue peptide San385
9YDQ 1.94 Å, Human delta opioid receptor complex with mini-Gi and agonist DADLE and allosteric…
9YDP 1.95 Å, Human delta opioid receptor complex with mini-Gi and agonist DADLE
6CRK 2.0 Å, Heterotrimeric G-protein in complex with an antibody fragment
8F0J 2.0 Å, Calcitonin Receptor in complex with Gs and Pramlintide analogue peptide San45
8F2B 2.0 Å, Amylin 3 Receptor in complex with Gs and Pramlintide analogue peptide San45
9XXT 2.0 Å, Cryo-EM structure of lysophosphatidylserine (18:0)-bound GPR174-Gs complex
6X18 2.1 Å, GLP-1 peptide hormone bound to Glucagon-Like peptide-1 (GLP-1) Receptor
6X19 2.1 Å, Non peptide agonist CHU-128, bound to Glucagon-Like peptide-1 (GLP-1) Receptor
9NTU 2.1 Å, Cryo-EM structure of BETP-GLP-1(9-36)-GLP-1R-Gs complex

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