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 journalArticlepeer-review

90 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 languageEnglish (US)
Pages (from-to)1345-1350
Number of pages6
JournalGenes and Development
Volume27
Issue number12
DOIs
StatePublished - Jun 15 2013

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Fingerprint Dive into the research topics of 'The structural basis of R-spondin recognition by LGR5 and RNF43'. Together they form a unique fingerprint.

Cite this