8AVO: Human leptin

Human leptin in complex with the human LEP-R ectodomain fused to a C-terminal trimeric isoleucine GCN4 zipper (open 3:3 model). Determined by electron microscopy at 6.84 Å resolution. Released 5 Apr 2023.

Method: Electron microscopy
Resolution: 6.84 Å
Organism: Homo sapiens
Chains: 6
Atoms: 17,811
Mol. weight: 352.28 kDa
Released: 5 Apr 2023

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

Secondary structure: helices and β-sheets

8AVO contains 69 α-helices and 175 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: 7 helices, 1 β-strand

Element	Residues	Length	Sheet
α-helix	24-44	21
α-helix	46-49	4
β-strand	57-58	2	1
α-helix	60-62	3
α-helix	72-88	17
α-helix	92-114	23
α-helix	131-137	7
α-helix	139-160	22

Chain B: 16 helices, 58 β-strands

Element	Residues	Length	Sheet
α-helix	237-240	4
β-strand	241-247	7	2
β-strand	253-258	6	2
β-strand	267-276	10	3
β-strand	281-288	8	3
β-strand	292-295	4	2
α-helix	298-299	2
β-strand	303-312	10	3
α-helix	319-325	7
β-strand	326-329	4	3
β-strand	333-336	4	4
β-strand	339-342	4	5
β-strand	348-354	7	4
β-strand	355	1	6
β-strand	360	1	6
α-helix	361-362	2
β-strand	366-370	5	5
β-strand	374-375	2	5
α-helix	376-377	2
β-strand	381-383	3	4
β-strand	389-393	5	4
α-helix	396-401	6
β-strand	402	1	7
β-strand	405	1	7
β-strand	408-414	7	5
β-strand	417	1	5
β-strand	418	1	8
β-strand	423-427	5	5
β-strand	434-438	5	9
β-strand	445-450	6	9
α-helix	452-454	3
β-strand	461-468	8	10
β-strand	472	1	11
β-strand	484-486	3	10
β-strand	489-490	2	9
β-strand	495-500	6	9
β-strand	507	1	11
β-strand	509-516	8	10
β-strand	521-523	3	10
α-helix	524-526	3
β-strand	527-529	3	10
α-helix	531-533	3
β-strand	541-547	7	12
β-strand	553-559	7	12
β-strand	568-576	9	13
α-helix	583	1
β-strand	584-588	5	13
β-strand	595-599	5	12
β-strand	607-615	9	13
α-helix	623-625	3
α-helix	627-628	2
β-strand	629-630	2	13
β-strand	641	1	14
α-helix	642-644	3
β-strand	645-650	6	15
β-strand	658-664	7	15
α-helix	665-667	3
β-strand	678-685	8	16
β-strand	689-696	8	16
β-strand	700-705	6	15
β-strand	709-717	9	16
β-strand	722	1	16
β-strand	725	1	14
β-strand	728-732	5	16
α-helix	735-737	3
β-strand	741-748	8	17
β-strand	754-760	7	17
β-strand	767-776	10	18
β-strand	784-789	6	18
β-strand	794-797	4	17
β-strand	807-815	9	18
β-strand	819	1	18
α-helix	821-822	2
β-strand	823-825	3	18

Chain C: 7 helices, 1 β-strand

Element	Residues	Length	Sheet
α-helix	24-44	21
α-helix	46-49	4
β-strand	57	1	8
α-helix	60-62	3
α-helix	72-88	17
α-helix	92-114	23
α-helix	131-137	7
α-helix	139-160	22

Chain D: 16 helices, 57 β-strands

Element	Residues	Length	Sheet
α-helix	237-240	4
β-strand	241-247	7	19
β-strand	253-258	6	19
β-strand	267-276	10	20
β-strand	281-288	8	20
β-strand	292-295	4	19
α-helix	298-299	2
β-strand	303-312	10	20
α-helix	319-325	7
β-strand	326-329	4	20
β-strand	333-336	4	21
β-strand	339-342	4	22
β-strand	348-354	7	21
β-strand	355	1	23
β-strand	360	1	23
α-helix	361-362	2
β-strand	366-370	5	22
β-strand	374-375	2	22
α-helix	376-377	2
β-strand	381-383	3	21
β-strand	389-393	5	21
α-helix	396-401	6
β-strand	402	1	24
β-strand	405	1	24
β-strand	408-414	7	22
β-strand	417	1	22
β-strand	423-427	5	22
β-strand	434-438	5	25
β-strand	445-450	6	25
α-helix	452-454	3
β-strand	461-468	8	26
β-strand	472	1	27
β-strand	484-486	3	26
β-strand	489-490	2	25
β-strand	495-500	6	25
β-strand	507	1	27
β-strand	509-516	8	26
β-strand	521-523	3	26
α-helix	524-526	3
β-strand	527-529	3	26
α-helix	531-533	3
β-strand	541-547	7	28
β-strand	553-559	7	28
β-strand	568-576	9	29
α-helix	583	1
β-strand	584-588	5	29
β-strand	595-599	5	28
β-strand	607-615	9	29
α-helix	623-625	3
α-helix	627-628	2
β-strand	629-630	2	29
β-strand	641	1	30
α-helix	642-644	3
β-strand	645-650	6	31
β-strand	658-664	7	31
α-helix	665-667	3
β-strand	678-685	8	32
β-strand	689-696	8	32
β-strand	700-705	6	31
β-strand	709-717	9	32
β-strand	722	1	32
β-strand	725	1	30
β-strand	728-732	5	32
α-helix	735-737	3
β-strand	741-748	8	33
β-strand	754-760	7	33
β-strand	767-776	10	34
β-strand	784-789	6	34
β-strand	794-797	4	33
β-strand	807-815	9	34
β-strand	819	1	34
α-helix	821-822	2
β-strand	823-825	3	34

Chain E: 7 helices, 0 β-strands

Element	Residues	Length
α-helix	24-44	21
α-helix	46-49	4
α-helix	60-62	3
α-helix	72-88	17
α-helix	92-114	23
α-helix	131-137	7
α-helix	139-160	22

Chain F: 16 helices, 58 β-strands

Element	Residues	Length	Sheet
α-helix	237-240	4
β-strand	241-247	7	35
β-strand	253-258	6	35
β-strand	267-276	10	36
β-strand	281-288	8	36
β-strand	292-295	4	35
α-helix	298-299	2
β-strand	303-312	10	36
α-helix	319-325	7
β-strand	326-329	4	36
β-strand	333-336	4	37
β-strand	339-342	4	38
β-strand	348-354	7	37
β-strand	355	1	39
β-strand	360	1	39
α-helix	361-362	2
β-strand	366-370	5	38
β-strand	374-375	2	38
α-helix	376-377	2
β-strand	381-383	3	37
β-strand	389-393	5	37
α-helix	396-401	6
β-strand	402	1	40
β-strand	405	1	40
β-strand	408-414	7	38
β-strand	417	1	38
β-strand	418-419	2	1
β-strand	423-427	5	38
β-strand	434-438	5	41
β-strand	445-450	6	41
α-helix	452-454	3
β-strand	461-468	8	42
β-strand	472	1	43
β-strand	484-486	3	42
β-strand	489-490	2	41
β-strand	495-500	6	41
β-strand	507	1	43
β-strand	509-516	8	42
β-strand	521-523	3	42
α-helix	524-526	3
β-strand	527-529	3	42
α-helix	531-533	3
β-strand	541-547	7	44
β-strand	553-559	7	44
β-strand	568-576	9	45
α-helix	583	1
β-strand	584-588	5	45
β-strand	595-599	5	44
β-strand	607-615	9	45
α-helix	623-625	3
α-helix	627-628	2
β-strand	629-630	2	45
β-strand	641	1	46
α-helix	642-644	3
β-strand	645-650	6	47
β-strand	658-664	7	47
α-helix	665-667	3
β-strand	678-685	8	48
β-strand	689-696	8	48
β-strand	700-705	6	47
β-strand	709-717	9	48
β-strand	722	1	48
β-strand	725	1	46
β-strand	728-732	5	48
α-helix	735-737	3
β-strand	741-748	8	49
β-strand	754-760	7	49
β-strand	767-776	10	50
β-strand	784-789	6	50
β-strand	794-797	4	49
β-strand	807-815	9	50
β-strand	819	1	50
α-helix	821-822	2
β-strand	823-825	3	50

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Leptin	A, C, E	protein	171	Homo sapiens	P41159 (AlphaFold model)
Leptin receptor	B, D, F	protein	868	Homo sapiens	P48357 (AlphaFold model)

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

>8AVO_1 Leptin (chains A, C, E)
AHHHHHHPGGPGSENLYFQGGSTGGVPIQKVQDDTKTLIKTIVTRINDISHTQSVSSKQK
VTGLDFIPGLHPILTLSKMDQTLAVYQQILTSMPSRNVIQISNDLENLRDLLHVLAFSKS
CHLPWASGLETLDSLGGVLEASGYSTEVVALSRLQGSLQDMLWQLDLSPGC

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

>8AVO_2 Leptin receptor (chains B, D, F)
FNLSYPITPWRFKLSCMPPNSTYDYFLLPAGLSKNTSNSNGHYETAVEPKFNSSGTHFSN
LSKTTFHCCFRSEQDRNCSLCADNIEGKTFVSTVNSLVFQQIDANWNIQCWLKGDLKLFI
CYVESLFKNLFRNYNYKVHLLYVLPEVLEDSPLVPQKGSFQMVHCNCSVHECCECLVPVP
TAKLNDTLLMCLKITSGGVIFQSPLMSVQPINMVKPDPPLGLHMEITDDGNLKISWSSPP
LVPFPLQYQVKYSENSTTVIREADKIVSATSLLVDSILPGSSYEVQVRGKRLDGPGIWSD
WSTPRVFTTQDVIYFPPKILTSVGSNVSFHCIYKKENKIVPSKEIVWWMNLAEKIPQSQY
DVVSDHVSKVTFFNLNETKPRGKFTYDAVYCCNEHECHHRYAELYVIDVNINISCETDGY
LTKMTCRWSTSTIQSLAESTLQLRYHRSSLYCSDIPSIHPISEPKDCYLQSDGFYECIFQ
PIFLLSGYTMWIRINHSLGSLDSPPTCVLPDSVVKPLPPSSVKAEITINIGLLKISWEKP
VFPENNLQFQIRYGLSGKEVQWKMYEVYDAKSKSVSLPVPDLCAVYAVQVRCKRLDGLGY
WSNWSNPAYTVVMDIKVPMRGPEFWRIINGDTMKKEKNVTLLWKPLMKNDSLCSVQRYVI
NHHTSCNGTWSEDVGNHTKFTFLWTEQAHTVTVLAINSIGASVANFNLTFSWPMSKVNIV
QSLSAYPLNSSCVIVSWILSPSDYKLMYFIIEWKNLNEDGEIKWLRISSSVKKYYIHDHF
IPIEKYQFSLYPIFMEGVGKPKIINSFTQDDIEKHQSDSTGGSGGSGGSGGSGGSRMKQI
EDKIEEILSKIYHIENEIARIKKLIGER

Primary citation

Mechanism of receptor assembly via the pleiotropic adipokine Leptin. Tsirigotaki, A., Dansercoer, A., Verschueren, K.H.G. et al. Nat Struct Mol Biol (2023) 30:551-563. DOI 10.1038/s41594-023-00941-9 · PubMed

Other PDB entries of the same protein (UniProt P41159 (AlphaFold model), which also has an AlphaFold model), best resolution first:

1AX8 2.4 Å, Human obesity protein, leptin
9PUO 3.1 Å, Neutralizing monoclonal antibody Fab fragment bound to leptin
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.
8X81 3.77 Å, Structure of leptin-LepR trimer with a large gap
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…
8K6Z NMR structure of human leptin

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