8XUM: LGR4 with RSPO2

Structure of LGR4 with RSPO2. Determined by electron microscopy at 2.9 Å resolution. Released 15 Jan 2025.

Method: Electron microscopy
Resolution: 2.9 Å
Organisms: Camelus bactrianus, Homo sapiens
Chains: 3
Atoms: 7,359
Mol. weight: 144.93 kDa
Released: 15 Jan 2025

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

Secondary structure: helices and β-sheets

8XUM contains 21 α-helices and 52 β-strands across 3 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: 19 helices, 31 β-strands

Element	Residues	Length	Sheet
α-helix	34	1
β-strand	35-36	2	3
β-strand	41-43	3	3
β-strand	62-64	3	3
β-strand	72-73	2	4
β-strand	86-88	3	3
β-strand	96-97	2	4
β-strand	110-112	3	3
β-strand	120	1	5
β-strand	134-136	3	3
β-strand	144	1	5
β-strand	158-160	3	3
α-helix	171-176	6
β-strand	182-184	3	3
β-strand	192-193	2	6
β-strand	206-208	3	3
β-strand	216-217	2	6
β-strand	230-232	3	3
α-helix	241-242	2
α-helix	244-247	4
β-strand	253-255	3	3
β-strand	263-264	2	7
β-strand	277-279	3	3
β-strand	287-288	2	7
β-strand	303-305	3	8
β-strand	326-328	3	8
α-helix	339-342	4
β-strand	348-350	3	8
β-strand	370-372	3	8
β-strand	381	1	9
β-strand	394-396	3	8
β-strand	405	1	9
β-strand	418-420	3	8
β-strand	439-441	3	8
β-strand	462-464	3	8
α-helix	472-475	4
β-strand	521-522	2	8
α-helix	539-560	22
α-helix	561-565	5
α-helix	572-600	29
α-helix	605-607	3
α-helix	609-613	5
α-helix	616-648	33
α-helix	658-682	25
α-helix	704-731	28
α-helix	746-768	23
α-helix	769-771	3
α-helix	779-789	11
α-helix	792-803	12
α-helix	806-820	15

Chain B: 2 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	43-47	5	10
β-strand	51-55	5	10
β-strand	60-66	7	10
β-strand	69-75	7	10
β-strand	82-85	4	10
β-strand	91-95	5	10
β-strand	101-103	3	11
β-strand	112-113	2	11
α-helix	114	1
β-strand	118-120	3	12
β-strand	123-125	3	12
α-helix	128-129	2
β-strand	135	1	12
β-strand	140	1	12

Chain C: 0 helices, 9 β-strands

Element	Residues	Length	Sheet
β-strand	442-448	7	1
β-strand	459-464	6	2
β-strand	470-476	7	2
β-strand	482-484	3	2
β-strand	492-495	4	1
β-strand	502-508	7	1
β-strand	517-522	6	2
β-strand	539-540	2	2
β-strand	544-545	2	2

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
MB52	C	protein	110	Camelus bactrianus
Leucine-rich repeat-containing G-protein coupled receptor 4	A	protein	951	Homo sapiens	Q9BXB1 (AlphaFold model)
R-spondin-2	B	protein	243	Homo sapiens	Q6UXX9 (AlphaFold model)

Sequence of entity 1 (C), FASTA

>8XUM_1 MB52 (chains C)
GSLRLSCAASGYTYSPYCMGWFRQAPGKAREGVATVDLDGSTIYADSVKGRFTISQDNAK
NTLYLQMNSLKPEDTAMYYCASRTRAGVTCGLNWAIFSYWGQGTQVTVSS

Sequence of entity 2 (A), FASTA

>8XUM_2 Leucine-rich repeat-containing G-protein coupled receptor 4 (chains A)
MPGPLGLLCFLALGLLGSAGPSGAAPPLCAAPCSCDGDRRVDCSGKGLTAVPEGLSAFTQ
ALDISMNNITQLPEDAFKNFPFLEELQLAGNDLSFIHPKALSGLKELKVLTLQNNQLKTV
PSEAIRGLSALQSLRLDANHITSVPEDSFEGLVQLRHLWLDDNSLTEVPVHPLSNLPTLQ
ALTLALNKISSIPDFAFTNLSSLVVLHLHNNKIRSLSQHCFDGLDNLETLDLNYNNLGEF
PQAIKALPSLKELGFHSNSISVIPDGAFDGNPLLRTIHLYDNPLSFVGNSAFHNLSDLHS
LVIRGASMVQQFPNLTGTVHLESLTLTGTKISSIPNNLCQEQKMLRTLDLSYNNIRDLPS
FNGCHALEEISLQRNQIYQIKEGTFQGLISLRILDLSRNLIHEIHSRAFATLGPITNLDV
SFNELTSFPTEGLNGLNQLKLVGNFKLKEALAAKDFVNLRSLSVPYAYQCCAFWGCDSYA
NLNTEDNSLQDHSVAQEKGTADAANVTSTLENEEHSQIIIHCTPSTGAFKPCEYLLGSWM
IRLTVWFIFLVALFFNLLVILTTFASCTSLPSSKLFIGLISVSNLFMGIYTGILTFLDAV
SWGRFAEFGIWWETGSGCKVAGFLAVFSSESAIFLLMLATVERSLSAKDIMKNGKSNHLK
QFRVAALLAFLGATVAGCFPLFHRGEYSASPLCLPFPTGETPSLGFTVTLVLLNSLAFLL
MAVIYTKLYCNLEKEDLSENSQSSMIKHVAWLIFTNCIFFCPVAFFSFAPLITAISISPE
IMKSVTLIFFPLPACLNPVLYVFFNPKFKEDWKLLKRRVTKKSGSVSVSISSQGGCLEQD
FYYDCGMYSHLQGNLTVCDCCESFLLTKPVSCKHLIKSHSCPALAVASCQRPEGYWSDCG
TQSAHSDYADEEDSFVSDSSDQVQACGRACFYQSRGFPLVRYAYNLPRVKD

Sequence of entity 3 (B), FASTA

>8XUM_3 R-spondin-2 (chains B)
MQFRLFSFALIILNCMDYSHCQGNRWRRSKRASYVSNPICKGCLSCSKDNGCSRCQQKLF
FFLRREGMRQYGECLHSCPSGYYGHRAPDMNRCARCRIENCDSCFSKDFCTKCKVGFYLH
RGRCFDECPDGFAPLDETMECVEGCEVGHWSEWGTCSRNNRTCGFKWGLETRTRQIVKKP
VKDTILCPTIAESRRCKMTMRHCPGGKRTPKAKEKRNKKKKRKLIERAQEQHSVFLATDR
ANQ

Primary citation

Cryo-EM structure of the full-length LGR4-RSPOs complex and a targeting nanobody for anti-obesity therapy. Zhang, Z., Wang, L., Qiao, H. et al. Nat Commun (2025) 16:8406-8406. DOI 10.1038/s41467-025-63410-5 · 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
9UOK 3.05 Å, Structure of the complex of LGR4_ECD with Norrin
8XT9 3.1 Å, structure of LGR4
8XFS 3.2 Å, LGR4-RSPO2-ZNRF3 RING domain (1:2:2)
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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