Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
Wnts are secreted growth factors that have critical roles in cell fate determination and stem cell renewal. The Wnt/β-catenin pathway is initiated by binding of a Wnt protein to a Frizzled (Fzd) receptor and a coreceptor, LDL receptor-related protein 5 or 6 (LRP5/6). We report the 2.1 Å resolution crystal structure of a Drosophila WntD fragment encompassing the N-terminal domain and the linker that connects it to the C-terminal domain. Differences in the structures of WntD and Xenopus Wnt8, including the positions of a receptor-binding β hairpin and a large solvent-filled cavity in the helical core, indicate conformational plasticity in the N-terminal domain that may be important for Wnt-Frizzled specificity. Structure-based mutational analysis of mouse Wnt3a shows that the linker between the N- and C-terminal domains is required for LRP6 binding. These findings provide important insights into Wnt function and evolution.
Adams,
PHENIX: building new software for automated crystallographic structure determination.
2002, Pubmed
Adams,
PHENIX: building new software for automated crystallographic structure determination.
2002,
Pubmed Ahn,
Structural basis of Wnt signaling inhibition by Dickkopf binding to LRP5/6.
2011,
Pubmed Anderson,
Granulysin crystal structure and a structure-derived lytic mechanism.
2003,
Pubmed Baker,
Electrostatics of nanosystems: application to microtubules and the ribosome.
2001,
Pubmed Bazan,
Structural architecture and functional evolution of Wnts.
2012,
Pubmed Bejsovec,
Signaling activities of the Drosophila wingless gene are separately mutable and appear to be transduced at the cell surface.
1995,
Pubmed Bourhis,
Wnt antagonists bind through a short peptide to the first β-propeller domain of LRP5/6.
2011,
Pubmed Bourhis,
Reconstitution of a frizzled8.Wnt3a.LRP6 signaling complex reveals multiple Wnt and Dkk1 binding sites on LRP6.
2010,
Pubmed Brünger,
Crystallography & NMR system: A new software suite for macromolecular structure determination.
1998,
Pubmed Chen,
MolProbity: all-atom structure validation for macromolecular crystallography.
2010,
Pubmed Chen,
Structural and functional studies of LRP6 ectodomain reveal a platform for Wnt signaling.
2011,
Pubmed Cheng,
Crystal structures of the extracellular domain of LRP6 and its complex with DKK1.
2011,
Pubmed Ching,
Lipid-independent secretion of a Drosophila Wnt protein.
2008,
Pubmed Couso,
Notch is required for wingless signaling in the epidermis of Drosophila.
1994,
Pubmed Dundas,
CASTp: computed atlas of surface topography of proteins with structural and topographical mapping of functionally annotated residues.
2006,
Pubmed Emsley,
Coot: model-building tools for molecular graphics.
2004,
Pubmed Evans,
Scaling and assessment of data quality.
2006,
Pubmed Ganguly,
Drosophila WntD is a target and an inhibitor of the Dorsal/Twist/Snail network in the gastrulating embryo.
2005,
Pubmed Gordon,
WntD is a feedback inhibitor of Dorsal/NF-kappaB in Drosophila development and immunity.
2005,
Pubmed Holm,
Dali server: conservation mapping in 3D.
2010,
Pubmed Hoppler,
Expression of a dominant-negative Wnt blocks induction of MyoD in Xenopus embryos.
1996,
Pubmed
,
Xenbase Janda,
Structural basis of Wnt recognition by Frizzled.
2012,
Pubmed
,
Xenbase Kabsch,
Integration, scaling, space-group assignment and post-refinement.
2010,
Pubmed MacDonald,
Wnt/beta-catenin signaling: components, mechanisms, and diseases.
2009,
Pubmed
,
Xenbase McCoy,
Phaser crystallographic software.
2007,
Pubmed McElwain,
A suppressor/enhancer screen in Drosophila reveals a role for wnt-mediated lipid metabolism in primordial germ cell migration.
2011,
Pubmed Rosenbaum,
GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function.
2007,
Pubmed Takada,
Monounsaturated fatty acid modification of Wnt protein: its role in Wnt secretion.
2006,
Pubmed
,
Xenbase Willert,
Wnt proteins are lipid-modified and can act as stem cell growth factors.
2003,
Pubmed
,
Xenbase Willert,
Wnt proteins.
2012,
Pubmed Wu,
Ligand receptor interactions in the Wnt signaling pathway in Drosophila.
2002,
Pubmed
