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4bst

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Revision as of 13:14, 13 March 2019

Structure of the ectodomain of LGR5 in complex with R-spondin-1 (Fu1Fu2) in P6122 crystal form

Structural highlights

4bst is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4bso, 4bsp, 4bsr, 4bss, 4bsu
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[RSPO1_HUMAN] Palmoplantar keratoderma - XX sex reversal - predisposition to squamous cell carcinoma. Keratoderma, palmoplantar, with squamous cell carcinoma of skin and sex reversal (PKKSCC) [MIM:610644]: A recessive syndrome characterized by XX (female to male) SRY-independent sex reversal, palmoplantar hyperkeratosis and predisposition to squamous cell carcinoma of the skin. Note=The disease is caused by mutations affecting the gene represented in this entry.

Function

[LGR5_HUMAN] Orphan receptor. Stem cell marker of the intestinal epithelium and the hair follicle. Target gene of Wnt signaling. [RSPO1_HUMAN] Activator of the beta-catenin signaling cascade, leading to TCF-dependent gene activation. Acts both in the canonical Wnt/beta-catenin-dependent pathway and in non-canonical Wnt signaling pathway, probably by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. Acts as a ligand for frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway. Has a essential roles in ovary determination.^[1] ^[2]

Publication Abstract from PubMed

Leucine-rich repeat-containing G protein-coupled receptors 4-6 (LGR4-LGR6) are receptors for R-spondins, potent Wnt agonists that exert profound trophic effects on Wnt-driven stem cells compartments. We present crystal structures of a signaling-competent fragment of R-spondin 1 (Rspo1) at a resolution of 2.0 A and its complex with the LGR5 ectodomain at a resolution of 3.2 A. Ecto-LGR5 binds Rspo1 at its concave leucine-rich-repeat (LRR) surface, forming a dimeric 2:2 complex. Fully conserved residues on LGR4-LGR6 explain promiscuous binding of R-spondins. A phenylalanine clamp formed by Rspo1 Phe106 and Phe110 pinches Ala190 of LGR5 and is critical for binding. Mutations related to congenital anonychia reduce signaling, but not binding of Rspo1 to LGR5. Furthermore, antibody binding to the extended loop of the C-terminal LRR cap of LGR5 activates signaling in a ligand-independent manner. Thus, our data reveal binding of R-spondins to conserved sites on LGR4-LGR6 and, in analogy to FSHR and related receptors, suggest a direct signaling role for LGR4-LGR6 in addition to its formation of Wnt receptor and coreceptor complexes.

Structure of Stem Cell Growth Factor R-spondin 1 in Complex with the Ectodomain of Its Receptor LGR5.,Peng WC, de Lau W, Forneris F, Granneman JC, Huch M, Clevers H, Gros P Cell Rep. 2013 Jun 27;3(6):1885-92. doi: 10.1016/j.celrep.2013.06.009. PMID:23809763^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kim KA, Kakitani M, Zhao J, Oshima T, Tang T, Binnerts M, Liu Y, Boyle B, Park E, Emtage P, Funk WD, Tomizuka K. Mitogenic influence of human R-spondin1 on the intestinal epithelium. Science. 2005 Aug 19;309(5738):1256-9. PMID:16109882 doi:309/5738/1256
↑ Hao HX, Xie Y, Zhang Y, Charlat O, Oster E, Avello M, Lei H, Mickanin C, Liu D, Ruffner H, Mao X, Ma Q, Zamponi R, Bouwmeester T, Finan PM, Kirschner MW, Porter JA, Serluca FC, Cong F. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature. 2012 Apr 29;485(7397):195-200. doi: 10.1038/nature11019. PMID:22575959 doi:10.1038/nature11019
↑ Peng WC, de Lau W, Forneris F, Granneman JC, Huch M, Clevers H, Gros P. Structure of Stem Cell Growth Factor R-spondin 1 in Complex with the Ectodomain of Its Receptor LGR5. Cell Rep. 2013 Jun 27;3(6):1885-92. doi: 10.1016/j.celrep.2013.06.009. PMID:23809763 doi:10.1016/j.celrep.2013.06.009

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4bst"

@@ Line 1: / Line 1: @@
 ==Structure of the ectodomain of LGR5 in complex with R-spondin-1 (Fu1Fu2) in P6122 crystal form==
-<StructureSection load='4bst' size='340' side='right' caption='[[4bst]], [[Resolution|resolution]] 4.30&Aring;' scene=''>
+<StructureSection load='4bst' size='340' side='right'caption='[[4bst]], [[Resolution|resolution]] 4.30&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4bst]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BST OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BST FirstGlance]. <br>
@@ Line 26: / Line 26: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Clevers, H]]
 [[Category: Forneris, F]]

4bst

From Proteopedia

Revision as of 13:14, 13 March 2019

Structure of the ectodomain of LGR5 in complex with R-spondin-1 (Fu1Fu2) in P6122 crystal form

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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