8X81: Leptin-LepR trimer with a large gap

Structure of leptin-LepR trimer with a large gap. Determined by electron microscopy at 3.77 Å resolution. Released 7 Aug 2024.

Method: Electron microscopy
Resolution: 3.77 Å
Organism: Homo sapiens
Chains: 6
Atoms: 21,875
Mol. weight: 345.54 kDa
Ligands: NAG
Released: 7 Aug 2024

Explore 8X81 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8X81 contains 78 α-helices and 211 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: 21 helices, 72 β-strands

Element	Residues	Length	Sheet
β-strand	35-37	3	1
β-strand	89-92	4	1
β-strand	97-98	2	1
α-helix	117-122	6
β-strand	128-133	6	2
β-strand	140-145	6	2
β-strand	158-160	3	3
β-strand	163-164	2	4
α-helix	174-176	3
β-strand	182	1	4
α-helix	183	1
β-strand	185	1	3
β-strand	187-188	2	5
β-strand	194-195	2	5
α-helix	202-204	3
β-strand	210-211	2	4
β-strand	214-217	4	3
β-strand	220-223	4	3
α-helix	224-226	3
β-strand	227-228	2	4
α-helix	231-234	4
α-helix	237-240	4
β-strand	244-248	5	6
β-strand	252-256	5	6
β-strand	268-276	9	7
β-strand	281-288	8	7
β-strand	292-296	5	6
α-helix	298-299	2
β-strand	303-306	4	7
β-strand	308-311	4	7
β-strand	326-329	4	7
β-strand	333-336	4	8
β-strand	339-343	5	9
β-strand	348-354	7	8
β-strand	355-356	2	10
β-strand	359-360	2	10
α-helix	361-362	2
α-helix	363-365	3
β-strand	366-370	5	9
β-strand	374-375	2	9
α-helix	376-377	2
α-helix	378-380	3
β-strand	381-383	3	8
β-strand	389-393	5	8
β-strand	402	1	11
β-strand	405	1	11
β-strand	408-414	7	9
β-strand	418	1	12
β-strand	423-428	6	9
β-strand	434-438	5	13
β-strand	445-449	5	13
α-helix	452-456	5
β-strand	461-469	9	14
α-helix	472-473	2
β-strand	484	1	14
β-strand	489-490	2	13
β-strand	496-500	5	13
β-strand	508-517	10	14
β-strand	520-523	4	14
α-helix	524-526	3
β-strand	527-529	3	14
β-strand	535	1	13
α-helix	537-540	4
β-strand	544-547	4	15
α-helix	548	1
β-strand	553-557	5	15
β-strand	569-576	8	16
β-strand	584-588	5	16
β-strand	597-599	3	15
β-strand	607-614	8	16
α-helix	622-625	4
β-strand	629	1	16
β-strand	641	1	17
β-strand	645-649	5	18
β-strand	658-664	7	18
α-helix	665-668	4
β-strand	680-684	5	19
β-strand	693-694	2	19
β-strand	701-705	5	18
β-strand	710-715	6	19
β-strand	725	1	17
β-strand	730-731	2	19
α-helix	734-736	3
β-strand	743-748	6	20
β-strand	753-759	7	20
β-strand	769-776	8	21
α-helix	782-783	2
β-strand	784-789	6	21
β-strand	794-798	5	20
β-strand	807-813	7	21
β-strand	814	1	22
β-strand	819	1	22
β-strand	823-825	3	21

Chain B: 21 helices, 70 β-strands

Element	Residues	Length	Sheet
β-strand	36	1	23
β-strand	86-88	3	24
β-strand	90	1	23
β-strand	91-92	2	25
β-strand	97-98	2	25
α-helix	114-122	9
β-strand	128-129	2	26
β-strand	132	1	27
β-strand	133-134	2	28
α-helix	140	1
β-strand	141	1	27
β-strand	144-145	2	26
β-strand	160-161	2	29
β-strand	164	1	30
α-helix	174-176	3
β-strand	184-185	2	29
α-helix	186	1
β-strand	187-188	2	31
β-strand	194-195	2	31
α-helix	203-205	3
β-strand	210	1	30
β-strand	214-217	4	24
β-strand	220-223	4	24
α-helix	231-233	3
β-strand	235-236	2	28
α-helix	237-238	2
α-helix	240	1
α-helix	258-260	3
β-strand	267-268	2	32
β-strand	311-312	2	32
α-helix	323-325	3
β-strand	334	1	33
β-strand	339-343	5	34
β-strand	348	1	35
β-strand	352	1	36
β-strand	353	1	33
β-strand	356	1	37
β-strand	359	1	37
β-strand	367-370	4	38
β-strand	374-375	2	38
α-helix	378-380	3
β-strand	382-383	2	36
β-strand	389-390	2	36
β-strand	393	1	35
β-strand	410-413	4	38
β-strand	417-418	2	38
β-strand	423	1	38
β-strand	424-428	5	34
β-strand	435-438	4	39
β-strand	445-448	4	39
α-helix	454-456	3
β-strand	461-468	8	40
β-strand	484-486	3	40
β-strand	498-500	3	39
β-strand	509-517	9	40
β-strand	520-523	4	40
α-helix	524-526	3
β-strand	527-529	3	40
α-helix	531-534	4
β-strand	535	1	39
α-helix	537-540	4
β-strand	541-547	7	41
α-helix	548	1
β-strand	553-559	7	41
β-strand	568-576	9	42
β-strand	584-588	5	42
β-strand	595-599	5	41
β-strand	607-615	9	42
α-helix	624-628	5
β-strand	629-630	2	42
β-strand	641	1	43
β-strand	645-650	6	44
β-strand	658-664	7	44
α-helix	665-668	4
α-helix	669-672	4
β-strand	678-684	7	45
β-strand	693-696	4	45
β-strand	700-705	6	44
β-strand	709-717	9	45
β-strand	725	1	43
β-strand	728-732	5	45
α-helix	733-736	4
β-strand	745-748	4	46
β-strand	754-757	4	46
β-strand	767-776	10	47
α-helix	781-783	3
β-strand	784-789	6	47
β-strand	795-797	3	46
β-strand	807-815	9	47
β-strand	818-819	2	47
β-strand	825	1	47

Chain C: 21 helices, 67 β-strands

Element	Residues	Length	Sheet
β-strand	35-36	2	48
β-strand	85-88	4	49
β-strand	90-91	2	48
α-helix	114-121	8
β-strand	128-133	6	50
β-strand	140-145	6	50
β-strand	158-160	3	49
α-helix	174-177	4
β-strand	187-188	2	51
β-strand	194-195	2	51
α-helix	202-204	3
β-strand	211	1	52
β-strand	214-217	4	49
β-strand	220-223	4	49
α-helix	224-226	3
β-strand	227	1	52
α-helix	231-234	4
β-strand	235	1	50
α-helix	237-240	4
β-strand	241-247	7	53
β-strand	253-258	6	53
α-helix	259-260	2
β-strand	268-271	4	54
β-strand	275-276	2	55
β-strand	281-282	2	55
α-helix	298-299	2
β-strand	308-311	4	54
α-helix	319-325	7
β-strand	334-335	2	56
β-strand	341-343	3	57
β-strand	348-353	6	56
β-strand	355-356	2	58
β-strand	359-360	2	58
α-helix	361-362	2
α-helix	363-365	3
β-strand	366-370	5	59
β-strand	374	1	59
α-helix	378-380	3
β-strand	381-383	3	56
β-strand	389-393	5	56
β-strand	402	1	60
β-strand	405	1	60
β-strand	410-414	5	59
β-strand	417-418	2	59
β-strand	426-428	3	57
α-helix	436	1
β-strand	437-438	2	61
α-helix	439	1
β-strand	445-446	2	61
β-strand	448-449	2	62
α-helix	453-456	4
β-strand	461-469	9	63
β-strand	484	1	63
β-strand	490	1	62
β-strand	496-497	2	62
β-strand	500	1	61
β-strand	508-516	9	63
β-strand	517	1	64
β-strand	520	1	64
β-strand	523	1	63
α-helix	524-526	3
β-strand	527-529	3	63
α-helix	537-540	4
β-strand	544-547	4	65
β-strand	553-557	5	65
β-strand	568-576	9	66
β-strand	583-588	6	66
β-strand	595-599	5	65
β-strand	607-615	9	66
α-helix	630-633	4
β-strand	645-649	5	67
β-strand	658-664	7	67
α-helix	665-667	3
α-helix	669-672	4
β-strand	679-684	6	68
β-strand	691-694	4	68
β-strand	702-705	4	67
β-strand	711-716	6	68
α-helix	735-737	3
β-strand	741-748	8	69
β-strand	754-760	7	69
β-strand	769-776	8	70
β-strand	785-789	5	70
β-strand	794-797	4	69
β-strand	807-813	7	70
β-strand	814	1	71
β-strand	819	1	71
β-strand	823-825	3	70

Chain D: 6 helices, 0 β-strands

Element	Residues	Length
α-helix	25-29	5
α-helix	31-45	15
α-helix	72-87	16
α-helix	92-114	23
α-helix	144-158	15
α-helix	160-163	4

Chain E: 5 helices, 1 β-strand

Element	Residues	Length	Sheet
α-helix	24-43	20
β-strand	56-57	2	38
α-helix	72-86	15
α-helix	92-114	23
α-helix	126-128	3
α-helix	131-161	31

Chain F: 4 helices, 1 β-strand

Element	Residues	Length	Sheet
α-helix	24-43	20
β-strand	57	1	12
α-helix	72-87	16
α-helix	92-114	23
α-helix	129-160	32

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Leptin receptor	A, B, C	protein	829	Homo sapiens	P48357 (AlphaFold model)
Leptin	D, E, F	protein	167	Homo sapiens	P41159 (AlphaFold model)

Sequence of entity 1 (A, B, C), FASTA

>8X81_1 Leptin receptor (chains A, B, C)
AFNLSYPITPWRFKLSCMPPNSTYDYFLLPAGLSKNTSNSNGHYETAVEPKFNSSGTHFS
NLSKTTFHCCFRSEQDRNCSLCADNIEGKTFVSTVNSLVFQQIDANWNIQCWLKGDLKLF
ICYVESLFKNLFRNYNYKVHLLYVLPEVLEDSPLVPQKGSFQMVHCNCSVHECCECLVPV
PTAKLNDTLLMCLKITSGGVIFQSPLMSVQPINMVKPDPPLGLHMEITDDGNLKISWSSP
PLVPFPLQYQVKYSENSTTVIREADKIVSATSLLVDSILPGSSYEVQVRGKRLDGPGIWS
DWSTPRVFTTQDVIYFPPKILTSVGSNVSFHCIYKKENKIVPSKEIVWWMNLAEKIPQSQ
YDVVSDHVSKVTFFNLNETKPRGKFTYDAVYCCNEHECHHRYAELYVIDVNINISCETDG
YLTKMTCRWSTSTIQSLAESTLQLRYHRSSLYCSDIPSIHPISEPKDCYLQSDGFYECIF
QPIFLLSGYTMWIRINHSLGSLDSPPTCVLPDSVVKPLPPSSVKAEITINIGLLKISWEK
PVFPENNLQFQIRYGLSGKEVQWKMYEVYDAKSKSVSLPVPDLCAVYAVQVRCKRLDGLG
YWSNWSNPAYTVVMDIKVPMRGPEFWRIINGDTMKKEKNVTLLWKPLMKNDSLCSVQRYV
INHHTSCNGTWSEDVGNHTKFTFLWTEQAHTVTVLAINSIGASVANFNLTFSWPMSKVNI
VQSLSAYPLNSSCVIVSWILSPSDYKLMYFIIEWKNLNEDGEIKWLRISSSVKKYYIHDH
FIPIEKYQFSLYPIFMEGVGKPKIINSFTQDDIEKHQSDGTHHHHHHHH

Sequence of entity 2 (D, E, F), FASTA

>8X81_2 Leptin (chains D, E, F)
MHWGTLCGFLWLWPYLFYVQAVPIQKVQDDTKTLIKTIVTRINDISHTQSVSSKQKVTGL
DFIPGLHPILTLSKMDQTLAVYQQILTSMPSRNVIQISNDLENLRDLLHVLAFSKSCHLP
WASGLETLDSLGGVLEASGYSTEVVALSRLQGSLQDMLWQLDLSPGC

Ligands and cofactors

ID	Name	Formula	Copies
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	19

Primary citation

Structural plasticity of human leptin binding to its receptor LepR. Xie, Y.F., Li, X., Qi, J. et al. Hlife (2023) 1:115-123. DOI 10.1016/j.hlife.2023.10.010

Other PDB entries of the same protein (UniProt P48357 (AlphaFold model), which also has an AlphaFold model), best resolution first:

3V6O 1.95 Å, Leptin Receptor-antibody complex
6E2P 2.83 Å, Structure of human JAK2 FERM/SH2 in complex with Leptin Receptor
8X85 3.58 Å, Structure of leptin-LepR dimer
7Z3Q 3.62 Å, Crystal structure of the human leptin:LepR-CRH2 encounter complex to 3.6 A resolution.
8X80 3.88 Å, Structure of leptin-LepR trimer with a small gap
8AVE 5.62 Å, Human leptin in complex with the human LEP-R ectodomain fused to a C-terminal trimeric…
8AVF 6.45 Å, Human leptin in complex with the human LEP-R ectodomain fused to a C-terminal trimeric…
8AVO 6.84 Å, Human leptin in complex with the human LEP-R ectodomain fused to a C-terminal trimeric…

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