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Significance Adenomatosis polyposis coli down-regulated 1 (APCDD1)—a conserved single-span transmembrane protein containing a large extracellular domain—negatively regulates WNT signaling and plays important roles in hair follicle development, CNS vascular development,… Click to show full abstract
Significance Adenomatosis polyposis coli down-regulated 1 (APCDD1)—a conserved single-span transmembrane protein containing a large extracellular domain—negatively regulates WNT signaling and plays important roles in hair follicle development, CNS vascular development, and glial differentiation. We report here the three-dimensional structure of the ECD of APCDD1, revealing an unusual architecture. The APCDD1 ECD consists of two closely apposed β-barrel domains (ABD1 and ABD2). ABD2 contains a large hydrophobic pocket that accommodates a bound lipid. In an in vitro assay, the ECD of APCDD1 bound to WNT7A, which contains a covalently linked palmitoleate. Collectively, the results of this study suggest that APCDD1 serves as a negative feedback regulator of WNT signaling by neutralizing WNT ligands.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2023
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