[HTML][HTML] Extracellular modulators of Wnt signalling
T Malinauskas, EY Jones - Current opinion in structural biology, 2014 - Elsevier
Current opinion in structural biology, 2014•Elsevier
Highlights•Structure and binding of lipid-modified Wnt8 with Frizzled8 cysteine-rich
domain.•Modularity of Wnt inhibitory factor 1 combining Wnt-binding and heparan sulphate-
binding.•Integration of multiple interaction sites in LRP5/6 ectodomain architecture.•Ternary
complex assembly of RNF43/ZNRF3 and LGR4/5/6 bridged by R-spondin.•Ectodomain
dimerisation of the Frizzled-specific E3 ligase ZNRF3.Wnt morphogens are secreted
signalling proteins that play leading roles in embryogenesis and tissue homeostasis …
domain.•Modularity of Wnt inhibitory factor 1 combining Wnt-binding and heparan sulphate-
binding.•Integration of multiple interaction sites in LRP5/6 ectodomain architecture.•Ternary
complex assembly of RNF43/ZNRF3 and LGR4/5/6 bridged by R-spondin.•Ectodomain
dimerisation of the Frizzled-specific E3 ligase ZNRF3.Wnt morphogens are secreted
signalling proteins that play leading roles in embryogenesis and tissue homeostasis …
Highlights
- Structure and binding of lipid-modified Wnt8 with Frizzled8 cysteine-rich domain.
- Modularity of Wnt inhibitory factor 1 combining Wnt-binding and heparan sulphate-binding.
- Integration of multiple interaction sites in LRP5/6 ectodomain architecture.
- Ternary complex assembly of RNF43/ZNRF3 and LGR4/5/6 bridged by R-spondin.
- Ectodomain dimerisation of the Frizzled-specific E3 ligase ZNRF3.
Wnt morphogens are secreted signalling proteins that play leading roles in embryogenesis and tissue homeostasis throughout life. Wnt signalling is controlled by multiple mechanisms, including posttranslational modification of Wnts, antagonist binding (to Wnts or their receptors), and regulation of the availability of Wnt receptors. Recent crystallographic, structure-guided biophysical and cell-based studies have advanced our understanding of how Wnt signalling is regulated at the cell surface. Structures include Wnt in complex with the cysteine-rich domain (CRD) of Frizzled, extracellular fragments of Wnt co-receptor LRP6, LRP6-binding antagonists Dickkopf and Sclerostin, antagonists 5T4/WAIF1 and Wnt inhibitory factor 1 (WIF-1), as well as Frizzled–ubiquitin ligases ZNRF3/RNF43 (in isolation and in complexes with Wnt signalling promoters R-spondins and LGR5). We review recent discoveries and remaining questions.
Elsevier