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This Podcast features an interview with Christopher Garcia, senior author of a Research Article published on 31 May 2012 in Science Express. Wnt signaling plays an important role in many developmental and homeostatic processes as well as in several types of cancer. Despite intensive study for many years, the structure of Wnts and information about how Wnts bind to their receptors, the Frizzled (Fz) proteins, have remained elusive. Garcia’s group has solved the crystal structure of a Wnt-Fz complex. The Wnt ligand formed a pincer-like two-domain structure that contacts opposite sides of Fz. Wnt ligands are lipidated, and the crystal structure also revealed that the lipid moiety covalently attached to Wnt participates in binding to Fz and could play an important role in ligand-receptor docking.