Insights into Wnt binding and signalling from the structures of two Frizzled cysteine-rich domains

Charles E. Dann, Jen-Chih Hsieh, Amir Rattner, Divya Sharma, Jeremy Nathans and Daniel J. Leahy ()
Additional contact information
Charles E. Dann: Department of Biophysics and Biophysical Chemistry
Jen-Chih Hsieh: Department of Molecular Biology and Genetics
Amir Rattner: Department of Molecular Biology and Genetics
Divya Sharma: Department of Biophysics and Biophysical Chemistry
Jeremy Nathans: Department of Molecular Biology and Genetics
Daniel J. Leahy: Department of Biophysics and Biophysical Chemistry

Nature, 2001, vol. 412, issue 6842, 86-90

Abstract: Abstract Members of the Frizzled family of seven-pass transmembrane proteins serve as receptors for Wnt signalling proteins1. Wnt proteins have important roles in the differentiation and patterning of diverse tissues during animal development2,3, and inappropriate activation of Wnt signalling pathways is a key feature of many cancers4. An extracellular cysteine-rich domain (CRD) at the amino terminus of Frizzled proteins binds Wnt proteins1, as do homologous domains in soluble proteins—termed secreted Frizzled-related proteins5—that function as antagonists of Wnt signalling6,7,8. Recently, an LDL-receptor-related protein has been shown to function as a co-receptor for Wnt proteins and to bind to a Frizzled CRD in a Wnt-dependent manner9,10,11. To investigate the molecular nature of the Wnt signalling complex, we determined the crystal structures of the CRDs from mouse Frizzled 8 and secreted Frizzled-related protein 3. Here we show a previously unknown protein fold, and the design and interpretation of CRD mutations that identify a Wnt-binding site. CRDs exhibit a conserved dimer interface that may be a feature of Wnt signalling. This work provides a framework for studies of homologous CRDs in proteins including muscle-specific kinase and Smoothened, a component of the Hedgehog signalling pathway12,13.

Date: 2001
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/35083601 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:412:y:2001:i:6842:d:10.1038_35083601

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/35083601

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().