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6c0b

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Structural basis for recognition of frizzled proteins by Clostridium difficile toxin B

Structural highlights

6c0b is a 2 chain structure with sequence from "bacillus_difficilis"_hall_and_o'toole_1935 "bacillus difficilis" hall and o'toole 1935 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	tcdB ("Bacillus difficilis" Hall and O'Toole 1935), FZD2 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[FZD2_HUMAN] Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues.

Publication Abstract from PubMed

Clostridium difficile infection is the most common cause of antibiotic-associated diarrhea in developed countries. The major virulence factor, C. difficile toxin B (TcdB), targets colonic epithelia by binding to the frizzled (FZD) family of Wnt receptors, but how TcdB recognizes FZDs is unclear. Here, we present the crystal structure of a TcdB fragment in complex with the cysteine-rich domain of human FZD2 at 2.5-angstrom resolution, which reveals an endogenous FZD-bound fatty acid acting as a co-receptor for TcdB binding. This lipid occupies the binding site for Wnt-adducted palmitoleic acid in FZDs. TcdB binding locks the lipid in place, preventing Wnt from engaging FZDs and signaling. Our findings establish a central role of fatty acids in FZD-mediated TcdB pathogenesis and suggest strategies to modulate Wnt signaling.

Structural basis for recognition of frizzled proteins by Clostridium difficile toxin B.,Chen P, Tao L, Wang T, Zhang J, He A, Lam KH, Liu Z, He X, Perry K, Dong M, Jin R Science. 2018 May 11;360(6389):664-669. doi: 10.1126/science.aar1999. PMID:29748286^[1]

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

References

↑ Chen P, Tao L, Wang T, Zhang J, He A, Lam KH, Liu Z, He X, Perry K, Dong M, Jin R. Structural basis for recognition of frizzled proteins by Clostridium difficile toxin B. Science. 2018 May 11;360(6389):664-669. doi: 10.1126/science.aar1999. PMID:29748286 doi:http://dx.doi.org/10.1126/science.aar1999

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6c0b"

@@ Line 1: / Line 1: @@
 ==Structural basis for recognition of frizzled proteins by Clostridium difficile toxin B==
-<StructureSection load='6c0b' size='340' side='right' caption='[[6c0b]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+<StructureSection load='6c0b' size='340' side='right'caption='[[6c0b]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[6c0b]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_difficilis"_hall_and_o'toole_1935 "bacillus difficilis" hall and o'toole 1935] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6C0B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6C0B FirstGlance]. <br>
@@ Line 25: / Line 25: @@
 [[Category: Bacillus difficilis hall and o'toole 1935]]
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Chen, P]]
 [[Category: Jin, R]]

6c0b

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Current revision

Structural basis for recognition of frizzled proteins by Clostridium difficile toxin B

Structural highlights

Function

Publication Abstract from PubMed

References

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