8XFS: LGR4-RSPO2-ZNRF3 RING domain

LGR4-RSPO2-ZNRF3 RING domain (1:2:2). Determined by electron microscopy at 3.2 Å resolution. Released 4 Dec 2024.

Method: Electron microscopy
Resolution: 3.2 Å
Organisms: Homo sapiens, Camelus bactrianus
Chains: 6
Atoms: 10,983
Mol. weight: 164.81 kDa
Released: 4 Dec 2024

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

Secondary structure: helices and β-sheets

8XFS contains 33 α-helices and 81 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: 17 helices, 32 β-strands

Element	Residues	Length	Sheet
β-strand	41-42	2	1
β-strand	61-63	3	1
β-strand	71-72	2	2
β-strand	85-87	3	1
β-strand	95-96	2	2
β-strand	109-111	3	1
β-strand	119	1	3
α-helix	122-125	4
β-strand	133-135	3	1
β-strand	143	1	3
β-strand	158-159	2	1
α-helix	170-173	4
β-strand	181-183	3	1
β-strand	191-192	2	4
β-strand	205-207	3	1
β-strand	215-216	2	4
β-strand	229-231	3	1
α-helix	243-246	4
β-strand	252-255	4	1
β-strand	262	1	5
β-strand	276-279	4	1
β-strand	286	1	5
β-strand	300-303	4	6
β-strand	323-326	4	6
β-strand	328	1	7
β-strand	347-350	4	6
β-strand	352	1	7
β-strand	369-372	4	6
β-strand	380	1	8
α-helix	382-385	4
β-strand	393-396	4	6
β-strand	404	1	8
β-strand	417-420	4	6
β-strand	438-440	3	6
α-helix	450-451	2
β-strand	461-463	3	6
α-helix	467-471	5
β-strand	521-522	2	6
α-helix	539-560	22
α-helix	561-566	6
α-helix	572-600	29
α-helix	605-612	8
α-helix	616-648	33
α-helix	658-682	25
α-helix	707-731	25
α-helix	743-767	25
α-helix	779-789	11
α-helix	792-804	13
α-helix	806-820	15

Chain B: 0 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	47	1	13
β-strand	51	1	13
β-strand	60-66	7	13
β-strand	69-75	7	13
β-strand	82-85	4	13
β-strand	92-95	4	13
β-strand	101-106	6	14
β-strand	109-113	5	14
β-strand	118-119	2	15
β-strand	124-125	2	15
β-strand	140	1	15

Chain C: 5 helices, 10 β-strands

Element	Residues	Length	Sheet
β-strand	60-68	9	9
β-strand	74-82	9	9
β-strand	84-85	2	9
β-strand	89	1	10
β-strand	94-101	8	9
β-strand	120-125	6	9
α-helix	129-131	3
α-helix	139-149	11
β-strand	151-157	7	9
α-helix	162-170	9
β-strand	176	1	10
β-strand	180-183	4	9
α-helix	185-197	13
β-strand	202-206	5	9
α-helix	218-239	22

Chain D: 1 helix, 10 β-strands

Element	Residues	Length	Sheet
β-strand	47	1	18
β-strand	51	1	18
β-strand	60-66	7	18
β-strand	69-75	7	18
β-strand	82-86	5	18
β-strand	91-95	5	18
β-strand	103	1	19
β-strand	112	1	19
β-strand	118	1	20
β-strand	125	1	20
α-helix	128-129	2

Chain E: 7 helices, 9 β-strands

Element	Residues	Length	Sheet
β-strand	58-69	12	16
β-strand	73-85	13	16
β-strand	89	1	17
β-strand	94-100	7	16
α-helix	103-105	3
α-helix	116-117	2
β-strand	120-125	6	16
α-helix	129-131	3
α-helix	139-149	11
β-strand	151-157	7	16
α-helix	162-170	9
β-strand	176	1	17
β-strand	180-183	4	16
α-helix	186-197	12
β-strand	203-206	4	16
α-helix	218-244	27

Chain F: 3 helices, 9 β-strands

Element	Residues	Length	Sheet
β-strand	443-448	6	11
β-strand	457-464	8	12
β-strand	470-475	6	12
β-strand	483-484	2	12
α-helix	486-488	3
β-strand	493-497	5	11
β-strand	502-507	6	11
α-helix	512-514	3
β-strand	516-523	8	12
α-helix	534-536	3
β-strand	539-540	2	12
β-strand	544-546	3	12

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Leucine-rich repeat-containing G-protein coupled receptor 4	A	protein	791	Homo sapiens	Q9BXB1 (AlphaFold model)
E3 ubiquitin-protein ligase ZNRF3	C, E	protein	190	Homo sapiens	Q9ULT6 (AlphaFold model)
nanobody Nb52	F	protein	106	Camelus bactrianus
R-spondin-2	B, D	protein	101	Homo sapiens	Q6UXX9 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8XFS_1 Leucine-rich repeat-containing G-protein coupled receptor 4 (chains A)
APCSCDGDRRVDCSGKGLTAVPEGLSAFTQALDISMNNITQLPEDAFANFPFLEELQLAG
NDLSFIHPKALSGLKELKVLTLQNNQLKTVPSEAIRGLSALQSLRLDANHITSVPEDSFE
GLVQLRHLWLDDNSLTEVPVHPLSNLPTLQALTLALNKISSIPDFAFTNLSSLVVLHLHN
NKIRSLSQHCFDGLDNLETLDLNYNNLGEFPQAIKALPSLKELGFHSNSISVIPDGAFDG
NPLLRTIHLYDNPLSFVGNSAFHNLSDLHSLVIRGASMVQQFPNLTGTVHLESLTLTGTK
ISSIPNNLCQEQKMLRTLDLSYNNIRDLPSFNGCHALEEISLQRNQIYQIKEGTFQGLIS
LRILDLSRNLIHEIHSRAFATLGPITNLDVSFNELTSFPTEGLNGLNQLKLVGNFKLKEA
LAAKDFVNLRSLSVPYAYQCCAFWGCDSYANLNTEDNSLQDHSVAQEKGTADAANVTSTL
ENEEHSQIIIHCTPSTGAFKPCEYLLGSWMIRLTVWFIFLVALFFNLLVILTTFASCTSL
PSSKLFIGLISVSNLFMGIYTGILTFLDAVSWGRFAEFGIWWETGSGCKVAGFLAVFSSE
SAIFLLMLATVERSLSAKDIMKNGKSNHLKQFRVAALLAFLGATVAGCFPLFHRGEYSAS
PLCLPFPTGETPSLGFTVTLVLLNSLAFLLMAVIYTKLYCNLEKEDLSENSQSSMIKHVA
WLIFTNCIFFCPVAFFSFAPLITAISISPEIMKSVTLIFFPLPACLNPVLYVFFNPKFKE
DWKLLKRRVTK

Sequence of entity 2 (C, E), FASTA

>8XFS_2 E3 ubiquitin-protein ligase ZNRF3 (chains C, E)
KETAFVEVVLFESSPSGDYTTYTTGLTGRFSRAGATLSAEGEIVQMHPLGLCNNNDEEDL
YEYGWVGVVKLEQPELDPKPCLTVLGKAKRAVQRGATAVIFDVSENPEAIDQLNQGSEDP
LKRPVVYVKGADAIKLMNIVNKQKVARARIQHRPPRQPTEYFDMGIFLAFFVVVSLVCLI
LLVKIKLKQR

Sequence of entity 3 (F), FASTA

>8XFS_3 nanobody Nb52 (chains F)
SLRLSCAASGYTYSPYCMGWFRQAPGKAREGVATVDLDGSTIYADSVKGRFTISQDNAKN
TLYLQMNSLKPEDTAMYYCASRTRAGVTCGLNWAIFSYWGQGTQVT

Sequence of entity 4 (B, D), FASTA

>8XFS_4 R-spondin-2 (chains B, D)
KGCLSCSKDNGCSRCQQKLFFFLRREGMRQYGECLHSCPSGYYGHRAPDMNRCARCRIEN
CDSCFSKDFCTKCKVGFYLHRGRCFDECPDGFAPLDETMEC

Primary citation

Structural insights into the LGR4-RSPO2-ZNRF3 complexes regulating WNT/ beta-catenin signaling. Wang, L., Hu, F., Cui, Q. et al. Nat Commun (2025) 16:362-362. DOI 10.1038/s41467-024-55431-3 · PubMed

Other PDB entries of the same protein (UniProt Q9BXB1 (AlphaFold model), which also has an AlphaFold model), best resolution first:

4QXE 2.2 Å, Crystal structure of LGR4 fused with hagfish VLR
4QXF 2.25 Å, crystal structure of human LGR4 and Rspo1
4KT1 2.5 Å, Complex of R-spondin 1 with LGR4 extracellular domain
9KGK 2.63 Å, Structure of the complex of LGR4 with NB18
8XUM 2.9 Å, Structure of LGR4 with RSPO2
9UOK 3.05 Å, Structure of the complex of LGR4_ECD with Norrin
8XT9 3.1 Å, structure of LGR4
8XFP 3.21 Å, the pentamerA complex of LGR4-RSPO2-ZNRF3(delta RING)
8XFT 3.24 Å, LGR4-RSPO2-ZNRF3(1:1:1)
9KB8 3.25 Å, Cryo-EM structure of LGR4-RSPO2-ZNRF3 complex (1:1:2)
8WVY 3.29 Å, Cryo-EM structure of LGR4 in complex with Norrin
8WVX 3.32 Å, Cryo-EM structure of LGR4 in complex with Norrin(dimer)

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