6L6R: LRP6 E1E2-SOST complex

Crystal structure of LRP6 E1E2-SOST complex. Determined by X-ray diffraction at 3.8 Å resolution. Released 28 Oct 2020.

Method: X-ray diffraction
Resolution: 3.8 Å
Organism: Homo sapiens
Chains: 4
Atoms: 11,314
Mol. weight: 179.36 kDa
Ligands: MG, NAG
Released: 28 Oct 2020

Explore 6L6R in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

6L6R contains 14 α-helices and 131 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, 57 β-strands

Element	Residues	Length	Sheet
β-strand	22-26	5	1
β-strand	28	1	2
β-strand	31-35	5	1
α-helix	43	1
β-strand	44-47	4	1
β-strand	53-59	7	2
β-strand	64-69	6	2
β-strand	74-79	6	2
β-strand	88-92	5	2
β-strand	100-103	4	3
β-strand	108-113	6	3
β-strand	118-123	6	3
β-strand	130-133	4	3
β-strand	140-146	7	4
β-strand	151-156	6	4
β-strand	162-167	6	4
β-strand	174-177	4	4
β-strand	184-190	7	5
β-strand	195-200	6	5
β-strand	205-210	6	5
β-strand	217-220	4	5
β-strand	227-233	7	6
β-strand	236-241	6	6
β-strand	246-251	6	6
β-strand	259-262	4	6
β-strand	271-274	4	1
α-helix	276-278	3
α-helix	290-292	3
β-strand	296-299	4	7
β-strand	306-309	4	7
α-helix	314-315	2
β-strand	316	1	8
β-strand	323	1	8
β-strand	329-335	7	9
β-strand	339-343	5	9
β-strand	351-354	4	9
β-strand	362-368	7	10
β-strand	373-378	6	10
β-strand	383-388	6	10
β-strand	395-398	4	10
β-strand	405-411	7	11
β-strand	416-421	6	11
β-strand	426-431	6	11
β-strand	438-441	4	11
β-strand	451-454	4	12
β-strand	459-462	4	12
β-strand	471-475	5	12
β-strand	482-485	4	12
β-strand	492-498	7	13
α-helix	499-501	3
β-strand	503-508	6	13
β-strand	513-518	6	13
β-strand	526-528	3	13
β-strand	535-540	6	14
β-strand	544-549	6	14
β-strand	554-559	6	14
β-strand	565-569	5	14
β-strand	575-582	8	9
α-helix	594-598	5
β-strand	602-604	3	15
β-strand	611-613	3	15
β-strand	619-620	2	16
β-strand	627-628	2	16

Chain B: 6 helices, 57 β-strands

Element	Residues	Length	Sheet
β-strand	22-26	5	17
β-strand	28	1	18
β-strand	31-35	5	17
α-helix	43	1
β-strand	44-47	4	17
β-strand	53-59	7	18
β-strand	64-69	6	18
β-strand	74-79	6	18
β-strand	88-92	5	18
β-strand	100-103	4	19
β-strand	108-113	6	19
β-strand	118-123	6	19
β-strand	130-133	4	19
β-strand	139-146	8	20
β-strand	151-157	7	20
β-strand	162-167	6	20
β-strand	174-177	4	20
β-strand	184-190	7	21
β-strand	195-200	6	21
β-strand	205-210	6	21
β-strand	217-220	4	21
β-strand	227-233	7	22
β-strand	236-241	6	22
β-strand	246-251	6	22
β-strand	259-262	4	22
β-strand	271-274	4	17
α-helix	276-278	3
α-helix	290-292	3
β-strand	296-299	4	23
β-strand	306-309	4	23
α-helix	314-315	2
β-strand	316	1	24
β-strand	323	1	24
β-strand	329-335	7	25
β-strand	339-343	5	25
β-strand	351-354	4	25
β-strand	362-368	7	26
β-strand	373-378	6	26
β-strand	384-387	4	26
β-strand	395-398	4	26
β-strand	405-411	7	27
β-strand	416-421	6	27
β-strand	426-431	6	27
β-strand	438-441	4	27
β-strand	451-454	4	28
β-strand	459-462	4	28
β-strand	471-475	5	28
β-strand	482-485	4	28
β-strand	492-498	7	29
α-helix	499-501	3
β-strand	503-508	6	29
β-strand	513-518	6	29
β-strand	526-528	3	29
β-strand	535-540	6	30
β-strand	544-549	6	30
β-strand	554-559	6	30
β-strand	565-569	5	30
β-strand	575-582	8	25
α-helix	594-598	5
β-strand	602-604	3	31
β-strand	611-613	3	31
β-strand	619-620	2	32
β-strand	627-628	2	32

Chain C: 1 helix, 9 β-strands

Element	Residues	Length	Sheet
β-strand	82-87	6	33
β-strand	90	1	34
β-strand	95-96	2	34
β-strand	100-105	6	33
α-helix	110-112	3
β-strand	134-136	3	35
β-strand	139-145	7	36
β-strand	146-147	2	34
β-strand	156-162	7	36
β-strand	165-167	3	35

Chain D: 1 helix, 8 β-strands

Element	Residues	Length	Sheet
β-strand	82-87	6	37
β-strand	90	1	38
β-strand	95-96	2	38
β-strand	100-105	6	37
α-helix	110-112	3
β-strand	134-136	3	39
β-strand	139-147	9	38
β-strand	155-162	8	38
β-strand	165-167	3	39

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Low-density lipoprotein receptor-related protein 6	A, B	protein	622	Homo sapiens	O75581 (AlphaFold model)
Sclerostin	C, D	protein	158	Homo sapiens	Q9BQB4 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>6L6R_1 Low-density lipoprotein receptor-related protein 6 (chains A, B)
ADPLLLYANRRDLRLVDATNGKENATIVVGGLEDAAAVDFVFSHGLIYWSDVSEEAIKRT
EFNKTESVQNVVVSGLLSPDGLACDWLGEKLYWTDSETNRIEVSNLDGSLRKVLFWQELD
QPRAIALDPSSGFMYWTDWGEVPKIERAGMDGSSRFIIINSEIYWPNGLTLDYEEQKLYW
ADAKLNFIHKSNLDGTNRQAVVKGSLPHPFALTLFEDILYWTDWSTHSILACNKYTGEGL
REIHSDIFSPMDIHAFSQQRQPNATNPCGIDNGGCSHLCLMSPVKPFYQCACPTGVKLLE
NGKTCKDGATELLLLARRTDLRRISLDTPDFTDIVLQLEDIRHAIAIDYDPVEGYIYWTD
DEVRAIRRSFIDGSGSQFVVTAQIAHPDGIAVDWVARNLYWTDTGTDRIEVTRLNGTMRK
ILISEDLEEPRAIVLDPMVGYMYWTDWGEIPKIERAALDGSDRVVLVNTSLGWPNGLALD
YDEGKIYWGDAKTDKIEVMNTDGTGRRVLVEDKIPHIFGFTLLGDYVYWTDWQRRSIERV
HKRSAEREVIIDQLPDLMGLKATNVHRVIGSNPCAEENGGCSHLCLYRPQGLRCACPIGF
ELISDMKTCIVPHHHHHHHHHH

Sequence of entity 2 (C, D), FASTA

>6L6R_2 Sclerostin (chains C, D)
GPSRQGWQAFKNDATEIIPELGEYPEPPPELENNKTMNRAENGGRPPHHPFETKDVSEYS
CRELHFTRYVTDGPCRSAKPVTELVCSGQCGPARLLPNAIGRGKWWRPSGPDFRCIPDRY
RAQRVQLLCPGGEAPRARKVRLVASCKCKRLTRFHNQS

Ligands and cofactors

ID	Name	Formula	Copies
MG	Magnesium ion	Mg	4
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	2

Water and common crystallization additives (ACT) are not listed.

Primary citation

Sclerostin inhibits Wnt signaling through tandem interaction with two LRP6 ectodomains. Kim, J., Han, W., Park, T. et al. Nat Commun (2020) 11:5357-5357. DOI 10.1038/s41467-020-19155-4 · PubMed

Other PDB entries of the same protein (UniProt O75581 (AlphaFold model), which also has an AlphaFold model), best resolution first:

3SOV 1.27 Å, The structure of a beta propeller domain in complex with peptide S
7NAM 1.6 Å, LRP6_E1 in complex with Lr-EET-3.5
8FFE 1.72 Å, Crystal structure of LRP6 E1E2 domains bound to YW210.09 Fab and engineered XWnt8 peptide
3SOB 1.9 Å, The structure of the first YWTD beta propeller domain of LRP6 in complex with a FAB
3SOQ 1.9 Å, The structure of the first YWTD beta propeller domain of LRP6 in complex with a DKK1…
4A0P 1.9 Å, Crystal structure of LRP6P3E3P4E4
8DVM 2.0 Å, Crystal structure of LRP6 E3E4 in complex with disulfide constrained peptide E3.6
4NM5 2.3 Å, Crystal structure of GSK-3/Axin complex bound to phosphorylated Wnt receptor LRP6 c-motif
4NM7 2.3 Å, Crystal structure of GSK-3/Axin complex bound to phosphorylated Wnt receptor LRP6 e-motif
8DVL 2.5 Å, Crystal structure of LRP6 E3E4 in complex with disulfide constrained peptide E3.18
5AIR 2.53 Å, Structural analysis of mouse GSK3beta fused with LRP6 peptide.
8DVN 2.53 Å, Crystal structure of LRP6 E3E4 in complex with disulfide constrained peptide E3.10

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