1IJY

CRYSTAL STRUCTURE OF THE CYSTEINE-RICH DOMAIN OF MOUSE FRIZZLED 8 (MFZ8)

Summary for 1IJY

• Entry DOI: 10.2210/pdb1ijy/pdb
• Related: 1IJX
• Descriptor: FRIZZLED HOMOLOG 8 (2 entities in total)
• Functional Keywords: wnt receptor, frizzled protein structure, cysteine-rich, signaling protein
• Biological source: Mus musculus (house mouse)
• Cellular location: Membrane; Multi-pass membrane protein: Q61091
• Total number of polymer chains: 2
• Total formula weight: 29886.12

Authors

Dann III, C.E.,Hsieh, J.C.,Rattner, A.,Sharma, D.,Nathans, J.,Leahy, D.J. (deposition date: 2001-05-01, release date: 2001-07-11, Last modification date: 2024-10-30)

Primary citation

Dann III, C.E.,Hsieh, J.C.,Rattner, A.,Sharma, D.,Nathans, J.,Leahy, D.J.
Insights into Wnt binding and signalling from the structures of two Frizzled cysteine-rich domains.
Nature, 412:86-90, 2001

PubMed Abstract: Members of the Frizzled family of seven-pass transmembrane proteins serve as receptors for Wnt signalling proteins. Wnt proteins have important roles in the differentiation and patterning of diverse tissues during animal development, and inappropriate activation of Wnt signalling pathways is a key feature of many cancers. An extracellular cysteine-rich domain (CRD) at the amino terminus of Frizzled proteins binds Wnt proteins, as do homologous domains in soluble proteins-termed secreted Frizzled-related proteins-that function as antagonists of Wnt signalling. 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 manner. 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 pathway.

PubMed: 11452312
DOI: 10.1038/35083601

Experimental method

X-RAY DIFFRACTION (1.35 Å)