The structural basis of R-spondin recognition by LGR5 and RNF43

Po Han Chen; Xiaoyan Chen; Zhenghong Lin; Deyu Fang; Xiaolin He

doi:10.1101/gad.219915.113

The structural basis of R-spondin recognition by LGR5 and RNF43

Po Han Chen, Xiaoyan Chen, Zhenghong Lin, Deyu Fang, Xiaolin He^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

103 Scopus citations

Abstract

R-spondins (RSPOs) enhance Wnt signaling, affect stem cell behavior, bind to leucine-rich repeat-containing G-proteincoupled receptors 4-6, (LGR4-6) and the transmembrane E3 ubiquitin ligases RING finger 43/zinc and RING finger 3 (RNF43/ZNRF3). The structure of RSPO1 bound to both LGR5 and RNF43 ectodomains confirms their physical linkage. RSPO1 is sandwiched by LGR5 and RNF43, with its rod module of the cysteine-rich domain (CRD) contacting LGR5 and a hairpin inserted into RNF43. LGR5 does not contact RNF43 but increases the affinity of RSPO1 to RNF43, supporting LGR5 as an engagement receptor and RNF43 as an effector receptor. Disease mutations map to the RSPO1- RNF43 interface, which promises therapeutic targeting.

Original language	English (US)
Pages (from-to)	1345-1350
Number of pages	6
Journal	Genes and Development
Volume	27
Issue number	12
DOIs	https://doi.org/10.1101/gad.219915.113
State	Published - Jun 15 2013

Keywords

E3 ubiquitin ligase
Furin-like repeat
LGR5
R-spondin
RNF43
Wnt signaling

ASJC Scopus subject areas

Genetics
Developmental Biology

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title = "The structural basis of R-spondin recognition by LGR5 and RNF43",

abstract = "R-spondins (RSPOs) enhance Wnt signaling, affect stem cell behavior, bind to leucine-rich repeat-containing G-proteincoupled receptors 4-6, (LGR4-6) and the transmembrane E3 ubiquitin ligases RING finger 43/zinc and RING finger 3 (RNF43/ZNRF3). The structure of RSPO1 bound to both LGR5 and RNF43 ectodomains confirms their physical linkage. RSPO1 is sandwiched by LGR5 and RNF43, with its rod module of the cysteine-rich domain (CRD) contacting LGR5 and a hairpin inserted into RNF43. LGR5 does not contact RNF43 but increases the affinity of RSPO1 to RNF43, supporting LGR5 as an engagement receptor and RNF43 as an effector receptor. Disease mutations map to the RSPO1- RNF43 interface, which promises therapeutic targeting.",

keywords = "E3 ubiquitin ligase, Furin-like repeat, LGR5, R-spondin, RNF43, Wnt signaling",

author = "Chen, {Po Han} and Xiaoyan Chen and Zhenghong Lin and Deyu Fang and Xiaolin He",

year = "2013",

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doi = "10.1101/gad.219915.113",

language = "English (US)",

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journal = "Genes and Development",

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T1 - The structural basis of R-spondin recognition by LGR5 and RNF43

AU - Chen, Po Han

AU - Chen, Xiaoyan

AU - Lin, Zhenghong

AU - Fang, Deyu

AU - He, Xiaolin

PY - 2013/6/15

Y1 - 2013/6/15

N2 - R-spondins (RSPOs) enhance Wnt signaling, affect stem cell behavior, bind to leucine-rich repeat-containing G-proteincoupled receptors 4-6, (LGR4-6) and the transmembrane E3 ubiquitin ligases RING finger 43/zinc and RING finger 3 (RNF43/ZNRF3). The structure of RSPO1 bound to both LGR5 and RNF43 ectodomains confirms their physical linkage. RSPO1 is sandwiched by LGR5 and RNF43, with its rod module of the cysteine-rich domain (CRD) contacting LGR5 and a hairpin inserted into RNF43. LGR5 does not contact RNF43 but increases the affinity of RSPO1 to RNF43, supporting LGR5 as an engagement receptor and RNF43 as an effector receptor. Disease mutations map to the RSPO1- RNF43 interface, which promises therapeutic targeting.

AB - R-spondins (RSPOs) enhance Wnt signaling, affect stem cell behavior, bind to leucine-rich repeat-containing G-proteincoupled receptors 4-6, (LGR4-6) and the transmembrane E3 ubiquitin ligases RING finger 43/zinc and RING finger 3 (RNF43/ZNRF3). The structure of RSPO1 bound to both LGR5 and RNF43 ectodomains confirms their physical linkage. RSPO1 is sandwiched by LGR5 and RNF43, with its rod module of the cysteine-rich domain (CRD) contacting LGR5 and a hairpin inserted into RNF43. LGR5 does not contact RNF43 but increases the affinity of RSPO1 to RNF43, supporting LGR5 as an engagement receptor and RNF43 as an effector receptor. Disease mutations map to the RSPO1- RNF43 interface, which promises therapeutic targeting.

KW - E3 ubiquitin ligase

KW - Furin-like repeat

KW - LGR5

KW - R-spondin

KW - RNF43

KW - Wnt signaling

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The structural basis of R-spondin recognition by LGR5 and RNF43

Abstract

Keywords

ASJC Scopus subject areas

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