8AVE: Human leptin

Human leptin in complex with the human LEP-R ectodomain fused to a C-terminal trimeric isoleucine GCN4 zipper (2:2 model). Determined by electron microscopy at 5.62 Å resolution. Released 5 Apr 2023.

Method: Electron microscopy
Resolution: 5.62 Å
Organism: Homo sapiens
Chains: 4
Atoms: 11,874
Mol. weight: 234.85 kDa
Released: 5 Apr 2023

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

Secondary structure: helices and β-sheets

8AVE contains 56 α-helices and 114 β-strands across 4 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: 6 helices, 0 β-strands

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

Chain B: 22 helices, 57 β-strands

Element	Residues	Length	Sheet
α-helix	237-240	4
β-strand	241-247	7	1
β-strand	253-258	6	1
α-helix	259-260	2
β-strand	267-276	10	2
β-strand	281-288	8	2
β-strand	292-295	4	1
α-helix	298-299	2
β-strand	303-312	10	2
α-helix	317-325	9
β-strand	326-329	4	2
β-strand	334-336	3	3
β-strand	339-342	4	4
β-strand	348-353	6	3
β-strand	355	1	5
β-strand	360	1	5
α-helix	361-362	2
β-strand	366-370	5	4
β-strand	374-375	2	4
α-helix	376-377	2
α-helix	378-380	3
β-strand	381-382	2	3
β-strand	389-393	5	3
α-helix	398-401	4
β-strand	402	1	6
β-strand	405	1	6
β-strand	408-414	7	4
β-strand	417	1	4
β-strand	418-419	2	7
β-strand	423-427	5	4
β-strand	434-438	5	8
β-strand	445-450	6	8
β-strand	462-468	7	9
β-strand	484-485	2	9
β-strand	488-490	3	8
β-strand	495-500	6	8
β-strand	509-517	9	9
β-strand	520-523	4	9
α-helix	524-526	3
β-strand	527-529	3	9
α-helix	531-534	4
β-strand	535	1	8
α-helix	537-540	4
β-strand	541-547	7	10
α-helix	548	1
β-strand	553-559	7	10
β-strand	568-576	9	11
α-helix	583	1
β-strand	584-588	5	11
β-strand	595-599	5	10
α-helix	606	1
β-strand	607-615	9	11
α-helix	622-628	7
β-strand	629-630	2	11
α-helix	631-633	3
β-strand	641	1	12
α-helix	642-644	3
β-strand	645-650	6	13
β-strand	658-664	7	13
α-helix	665-668	4
α-helix	669-672	4
β-strand	678-685	8	14
β-strand	689-696	8	14
β-strand	700-705	6	13
β-strand	709-717	9	14
β-strand	722	1	14
β-strand	725	1	12
β-strand	728-732	5	14
α-helix	735-737	3
β-strand	741-750	10	15
β-strand	753-760	8	15
β-strand	767-776	10	16
β-strand	784-789	6	16
β-strand	794-797	4	15
α-helix	806	1
β-strand	807-815	9	16
β-strand	818-819	2	16
α-helix	821-822	2
β-strand	823-825	3	16

Chain C: 6 helices, 1 β-strand

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

Chain D: 22 helices, 56 β-strands

Element	Residues	Length	Sheet
α-helix	237-240	4
β-strand	241-247	7	17
β-strand	253-258	6	17
α-helix	259-260	2
β-strand	267-276	10	18
β-strand	281-288	8	18
β-strand	292-295	4	17
α-helix	298-299	2
β-strand	303-312	10	18
α-helix	317-325	9
β-strand	326-329	4	18
β-strand	334-336	3	19
β-strand	339-342	4	20
β-strand	348-353	6	19
β-strand	355	1	21
β-strand	360	1	21
α-helix	361-362	2
β-strand	366-370	5	20
β-strand	374-375	2	20
α-helix	376-377	2
α-helix	378-380	3
β-strand	381-382	2	19
β-strand	389-393	5	19
α-helix	398-401	4
β-strand	402	1	22
β-strand	405	1	22
β-strand	408-414	7	20
β-strand	417	1	20
β-strand	423-427	5	20
β-strand	434-438	5	23
β-strand	445-450	6	23
β-strand	462-468	7	24
β-strand	484-485	2	24
β-strand	488-490	3	23
β-strand	495-500	6	23
β-strand	509-517	9	24
β-strand	520-523	4	24
α-helix	524-526	3
β-strand	527-529	3	24
α-helix	531-534	4
β-strand	535	1	23
α-helix	537-540	4
β-strand	541-547	7	25
α-helix	548	1
β-strand	553-559	7	25
β-strand	568-576	9	26
α-helix	583	1
β-strand	584-588	5	26
β-strand	595-599	5	25
α-helix	606	1
β-strand	607-615	9	26
α-helix	622-628	7
β-strand	629-630	2	26
α-helix	631-633	3
β-strand	641	1	27
α-helix	642-644	3
β-strand	645-650	6	28
β-strand	658-664	7	28
α-helix	665-668	4
α-helix	669-672	4
β-strand	678-685	8	29
β-strand	689-696	8	29
β-strand	700-705	6	28
β-strand	709-717	9	29
β-strand	722	1	29
β-strand	725	1	27
β-strand	728-732	5	29
α-helix	735-737	3
β-strand	741-750	10	30
β-strand	753-760	8	30
β-strand	767-776	10	31
β-strand	784-789	6	31
β-strand	794-797	4	30
α-helix	806	1
β-strand	807-815	9	31
β-strand	818-819	2	31
α-helix	821-822	2
β-strand	823-825	3	31

Molecules and chains

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

Sequence of entity 1 (A, C), FASTA

>8AVE_1 Leptin (chains A, C)
AHHHHHHPGGPGSENLYFQGGSTGGVPIQKVQDDTKTLIKTIVTRINDISHTQSVSSKQK
VTGLDFIPGLHPILTLSKMDQTLAVYQQILTSMPSRNVIQISNDLENLRDLLHVLAFSKS
CHLPWASGLETLDSLGGVLEASGYSTEVVALSRLQGSLQDMLWQLDLSPGC

Sequence of entity 2 (B, D), FASTA

>8AVE_2 Leptin receptor (chains B, D)
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
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…
8K6Z NMR structure of human leptin

Browse structure collections

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