6H15: LRP6 P3E3P4E4

Structure of LRP6 P3E3P4E4 in complex with VHH L-P2-B10. Determined by X-ray diffraction at 2.6 Å resolution. Released 30 Jan 2019.

Method: X-ray diffraction
Resolution: 2.6 Å
Organisms: Homo sapiens, Lama glama
Chains: 4
Atoms: 12,113
Mol. weight: 171.06 kDa
Ligands: NAG
Released: 30 Jan 2019

Explore 6H15 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

6H15 contains 20 α-helices and 136 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: 7 helices, 56 β-strands

Element	Residues	Length	Sheet
β-strand	633-638	6	1
β-strand	641-646	6	1
β-strand	654-655	2	1
β-strand	664-670	7	2
β-strand	675-680	6	2
β-strand	685-690	6	2
β-strand	697-700	4	2
β-strand	709-713	5	3
β-strand	718-723	6	3
β-strand	728-733	6	3
β-strand	740-743	4	3
β-strand	750-756	7	4
β-strand	761-766	6	4
β-strand	772-777	6	4
β-strand	784-787	4	4
β-strand	793-799	7	5
β-strand	804-809	6	5
β-strand	814-819	6	5
β-strand	826-829	4	5
β-strand	835-841	7	6
β-strand	844-849	6	6
β-strand	854-859	6	6
β-strand	867-871	5	6
β-strand	878-882	5	1
α-helix	884-886	3
α-helix	892-894	3
α-helix	896-899	4
β-strand	903-907	5	7
β-strand	911-915	5	7
β-strand	921-922	2	8
β-strand	929-930	2	8
β-strand	935-939	5	9
β-strand	944-947	4	9
α-helix	954-956	3
β-strand	957-958	2	9
β-strand	967-973	7	10
β-strand	978-983	6	10
β-strand	988-992	5	10
β-strand	1000-1003	4	10
β-strand	1016-1022	7	11
β-strand	1027-1032	6	11
β-strand	1037-1042	6	11
β-strand	1047-1052	6	11
β-strand	1059-1065	7	12
β-strand	1070-1077	8	12
β-strand	1080-1087	8	12
β-strand	1094-1097	4	12
β-strand	1104-1110	7	13
β-strand	1115-1120	6	13
β-strand	1125-1130	6	13
β-strand	1137-1140	4	13
β-strand	1147-1152	6	14
β-strand	1156-1161	6	14
β-strand	1166-1171	6	14
β-strand	1179-1183	5	14
β-strand	1190-1194	5	9
α-helix	1195-1197	3
α-helix	1199-1203	5
α-helix	1210-1213	4
β-strand	1217-1220	4	15
β-strand	1226-1229	4	15
β-strand	1235-1236	2	16
β-strand	1243-1244	2	16

Chain B: 6 helices, 56 β-strands

Element	Residues	Length	Sheet
β-strand	633-638	6	23
β-strand	641-646	6	23
β-strand	654-655	2	23
β-strand	664-670	7	24
β-strand	675-680	6	24
β-strand	685-690	6	24
β-strand	697-700	4	24
β-strand	707-713	7	25
β-strand	718-723	6	25
β-strand	728-733	6	25
β-strand	740-743	4	25
β-strand	750-756	7	26
β-strand	761-766	6	26
β-strand	772-777	6	26
β-strand	784-787	4	26
β-strand	793-799	7	27
β-strand	804-809	6	27
β-strand	814-819	6	27
β-strand	826-829	4	27
β-strand	835-841	7	28
β-strand	844-849	6	28
β-strand	854-859	6	28
β-strand	867-870	4	28
β-strand	879-882	4	23
α-helix	884-886	3
α-helix	892-896	5
α-helix	897-899	3
β-strand	903-907	5	29
β-strand	911-915	5	29
β-strand	921-922	2	30
β-strand	929-930	2	30
β-strand	935-940	6	31
β-strand	944-947	4	31
α-helix	954-956	3
β-strand	957-958	2	31
β-strand	967-973	7	32
β-strand	978-983	6	32
β-strand	988-992	5	32
β-strand	1000-1003	4	32
β-strand	1016-1022	7	33
β-strand	1027-1032	6	33
β-strand	1037-1042	6	33
β-strand	1047-1053	7	33
β-strand	1059-1065	7	34
β-strand	1070-1077	8	34
β-strand	1080-1087	8	34
β-strand	1094-1097	4	34
β-strand	1104-1110	7	35
β-strand	1115-1120	6	35
β-strand	1125-1130	6	35
β-strand	1137-1140	4	35
β-strand	1147-1152	6	36
β-strand	1156-1161	6	36
β-strand	1166-1171	6	36
β-strand	1179-1182	4	36
β-strand	1188-1194	7	31
α-helix	1199-1203	5
α-helix	1210-1213	4
β-strand	1217-1220	4	37
β-strand	1226-1229	4	37
β-strand	1235-1236	2	38
β-strand	1243-1244	2	38

Chain C: 4 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	4-8	5	17
β-strand	12-13	2	18
β-strand	19-26	8	17
α-helix	30-32	3
β-strand	34-40	7	19
β-strand	47-53	7	19
β-strand	59-61	3	19
α-helix	63-65	3
β-strand	69-73	5	17
β-strand	80-84	5	17
α-helix	89-91	3
β-strand	93-100	8	19
α-helix	110-112	3
β-strand	115-116	2	19
β-strand	120-122	3	19
β-strand	123-124	2	18

Chain D: 3 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	4-8	5	20
β-strand	12-13	2	21
β-strand	19-26	8	20
β-strand	34-40	7	22
β-strand	47-53	7	22
β-strand	59-61	3	22
α-helix	63-65	3
β-strand	69-73	5	20
β-strand	79-84	6	20
α-helix	89-91	3
β-strand	93-100	8	22
α-helix	110-112	3
β-strand	115-116	2	22
β-strand	120-122	3	22
β-strand	123-124	2	21

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Low-density lipoprotein receptor-related protein 6	A, B	protein	616	Homo sapiens	O75581 (AlphaFold model)
VHH L-P2-B10	C, D	protein	123	Lama glama

Sequence of entity 1 (A, B), FASTA

>6H15_1 Low-density lipoprotein receptor-related protein 6 (chains A, B)
PEAFLLFSRRADIRRISLETNNNNVAIPLTGVKEASALDFDVTDNRIYWTDISLKTISRA
FMNGSALEHVVEFGLDYPEGMAVDWLGKNLYWADTGTNRIEVSKLDGQHRQVLVWKDLDS
PRALALDPAEGFMYWTEWGGKPKIDRAAMDGSERTTLVPNVGRANGLTIDYAKRRLYWTD
LDTNLIESSNMLGLNREVIADDLPHPFGLTQYQDYIYWTDWSRRSIERANKTSGQNRTII
QGHLDYVMDILVFHSSRQSGWNECASSNGHCSHLCLAVPVGGFVCGCPAHYSLNADNRTC
SAPTTFLLFSQKSAINRMVIDEQQSPDIILPIHSLRNVRAIDYDPLDKQLYWIDSRQNMI
RKAQEDGSQGFTVVVSSVPSQNLEIQPYDLSIDIYSRYIYWTCEATNVINVTRLDGRSVG
VVLKGEQDRPRAVVVNPEKGYMYFTNLQERSPKIERAALDGTEREVLFFSGLSKPIALAL
DSRLGKLFWADSDLRRIESSDLSGANRIVLEDSNILQPVGLTVFENWLYWIDKQQQMIEK
IDMTGREGRTKVQARIAQLSDIHAVKELNLQEYRQHPCAQDNGGCSHICLVKGDGTTRCS
CPMHLVLLQDELSCGA

Sequence of entity 2 (C, D), FASTA

>6H15_2 VHH L-P2-B10 (chains C, D)
VQLQESGGCLVQAGGSLRLSCAASGSTFSTYTIGWFRQAPGKEREFVAAIHWDGGQTYYA
DSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCAARGRRYFDFTYSDVYDYWGQGTQV
TVS

Ligands and cofactors

ID	Name	Formula	Copies
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	5

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

Primary citation

Anti-LRP5/6 VHHs promote differentiation of Wnt-hypersensitive intestinal stem cells. Fenderico, N., van Scherpenzeel, R.C., Goldflam, M. et al. Nat Commun (2019) 10:365-365. DOI 10.1038/s41467-018-08172-z · 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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