The structural biology of canonical Wnt signalling
The structural biology of canonical Wnt signalling
The Wnt signalling pathways are of great importance in embryonic development and oncogenesis. Canonical and non-canonical Wnt signalling pathways are known, with the canonical (or β-catenin dependent) pathway being perhaps the best studied of these. While structural knowledge of proteins and interactions involved in canonical Wnt signalling has accumulated over the past 20 years, the pace of discovery has increased in recent years, with the structures of several key proteins and assemblies in the pathway being released. In this review, we provide a brief overview of canonical Wnt signalling, followed by a comprehensive overview of currently available X-ray, NMR and cryoEM data elaborating the structures of proteins and interactions involved in canonical Wnt signalling. While the volume of structures available is considerable, numerous gaps in knowledge remain, particularly a comprehensive understanding of the assembly of large multiprotein complexes mediating key aspects of pathway, as well as understanding the structure and activation of membrane receptors in the pathway. Nonetheless, the presently available data affords considerable opportunities for structure-based drug design efforts targeting canonical Wnt signalling.
- University of Edinburgh United Kingdom
- Curtin University Australia
- Universtity of Edinburgh United Kingdom
- Institute of Genetics and Cancer United Kingdom
- Edinburgh Cancer Research Centre United Kingdom
Cell Nucleus, Wnt Proteins, Protein Conformation, Drug Design, Animals, Humans, Receptors, Cell Surface, Review Articles, Wnt Signaling Pathway
Cell Nucleus, Wnt Proteins, Protein Conformation, Drug Design, Animals, Humans, Receptors, Cell Surface, Review Articles, Wnt Signaling Pathway
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