PMID: 23756651

 

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

Abstract :

1. R-spondins (RSPOs) enhance Wnt signaling, affect stem cell behavior, bind to leucine leucine-rich repeat-containing G-protein-coupled receptors 4-6 , ( LGR4-6 ) and the transmembrane E3 ubiquitin ligases RING finger 43/zinc and RING finger 3 (RNF43 / ZNRF3 )
2. The structure of RSPO1 bound to both LGR5 and RNF43 ectodomains confirms their physical linkage
3. 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
4. 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
5. Disease mutations map to the RSPO1- RNF43 interface, which promises therapeutic targeting