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

Science
Peng ChenRongsheng Jin

Abstract

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.

References

Apr 16, 2005·Clinical Microbiology Reviews·Daniel E Voth, Jimmy D Ballard
Apr 19, 2005·Genes & Development·Alex Gregorieff, Hans Clevers
Jul 22, 2006·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Denise DrudyLorraine Kyne
Dec 5, 2006·Developmental Cell·Ritsuko TakadaShinji Takada
Apr 9, 2008·Trends in Microbiology·Thomas Jank, Klaus Aktories
Mar 3, 2009·Nature·Dena LyrasJulian I Rood
Jun 17, 2009·Nature Reviews. Microbiology·Maja RupnikDale N Gerding
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Aug 11, 2010·The American Journal of the Medical Sciences·Latisha Heinlen, Jimmy D Ballard
Sep 17, 2010·Nature·Sarah A KuehneNigel P Minton
Jul 1, 2010·Toxins·Xingmin SunHanping Feng
Jun 2, 2012·Science·Claudia Y JandaK Christopher Garcia
Aug 25, 2012·Frontiers in Cellular and Infection Microbiology·Rory N Pruitt, D Borden Lacy
Dec 5, 2012·Cold Spring Harbor Perspectives in Biology·Bryan T MacDonald, Xi He
Dec 4, 2013·Microbiology and Molecular Biology Reviews : MMBR·Jonathan J Hunt, Jimmy D Ballard
Jun 4, 2015·Proceedings of the National Academy of Sciences of the United States of America·Michelle E LaFranceD Borden Lacy
Mar 13, 2016·Current Topics in Developmental Biology·Yanshu WangJeremy Nathans
May 10, 2016·Nature Reviews. Disease Primers·Wiep Klaas SmitsEd J Kuijper
Aug 12, 2016·Nature Microbiology·Nicole M ChumblerD Borden Lacy
Aug 31, 2016·Nature Microbiology·Nicole M ChumblerD Borden Lacy
Apr 6, 2017·Proceedings of the National Academy of Sciences of the United States of America·Aaron H NileRami N Hannoush
May 27, 2017·Genes & Development·Zachary J DeBruineKarsten Melcher
Aug 27, 2017·The Journal of Biological Chemistry·Pulkit GuptaRoman A Melnyk

❮ Previous
Next ❯

Citations

Dec 12, 2018·The Journal of Biological Chemistry·Aaron H Nile, Rami N Hannoush
Jul 17, 2019·Nature Structural & Molecular Biology·Peng ChenRongsheng Jin
Jul 30, 2020·Biochemical Society Transactions·Mark Agostino, Sebastian Öther-Gee Pohl
Jul 20, 2018·Frontiers in Microbiology·Dennis SchöttelndreierHarald Genth
Oct 6, 2018·Science·Anselm Sommer, Mark A Lemmon
Nov 13, 2018·Frontiers in Microbiology·Soo-Young ChungRalf Gerhard
Dec 12, 2018·Infection and Immunity·Lauren E Hartley-TassellMichael P Jennings
Nov 30, 2019·Frontiers in Immunology·Johanna K LjungbergAntje Blumenthal
Nov 5, 2019·Frontiers in Immunology·Madison R RoganJere W McBride
Mar 22, 2020·Proceedings of the National Academy of Sciences of the United States of America·Steven J MiletoDena Lyras
Apr 1, 2020·American Journal of Physiology. Gastrointestinal and Liver Physiology·Melinda A EngevikJames Versalovic
Sep 21, 2020·Signal Transduction and Targeted Therapy·Klaus Aktories
Oct 16, 2019·Frontiers in Immunology·Octavio Silva-GarcíaVíctor M Baizabal-Aguirre
Dec 20, 2019·Nature Reviews. Immunology·Yotam E Bar-EphraimHans Clevers
Mar 5, 2021·International Journal of Biological Macromolecules·Shifeng XiaoChengchen Wu
Apr 22, 2021·The FEBS Journal·Franz WaiblBernhard Rupp
Jun 3, 2021·Microbiology and Molecular Biology Reviews : MMBR·Kathleen E Orrell, Roman A Melnyk
Aug 26, 2021·Trends in Biochemical Sciences·Kathleen E Orrell, Roman A Melnyk
Feb 13, 2020·Journal of Medicinal Chemistry·Yuguang ZhaoE Yvonne Jones
Nov 25, 2021·EMBO Reports·Aria AminzadehRené Jørgensen
Nov 28, 2021·Nature Reviews. Microbiology·Shannon L KordusD Borden Lacy
Dec 22, 2021·Molecular Microbiology·Carmen KlepkaRalf Gerhard
Oct 28, 2021·The EMBO Journal·Andrew E RosselotChristian I Hong

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bacterial Protein Structures

Bacterial protein structures can expedite the development of novel antibiotics. Here is the latest research on bacterial proteins and the resolution of their structures.

Bacterial Protein Structures (ASM)

Bacterial protein structures can expedite the development of novel antibiotics. Here is the latest research on bacterial proteins and the resolution of their structures.