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Janda CY
,
Waghray D
,
Levin AM
,
Thomas C
,
Garcia KC
.
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Wnts are lipid-modified morphogens that play critical roles in development principally through engagement of Frizzled receptors. The 3.25 angstrom structure of Xenopus Wnt8 (XWnt8) in complex with mouse Frizzled-8 (Fz8) cysteine-rich domain (CRD) reveals an unusual two-domain Wnt structure, not obviously related to known protein folds, resembling a "hand" with "thumb" and "index" fingers extended to grasp the Fz8-CRD at two distinct binding sites. One site is dominated by a palmitoleic acid lipid group projecting from serine 187 at the tip of Wnt's thumb into a deep groove in the Fz8-CRD. In the second binding site, the conserved tip of Wnt's "index finger" forms hydrophobic amino acid contacts with a depression on the opposite side of the Fz8-CRD. The conservation of amino acids in both interfaces appears to facilitate ligand-receptor cross-reactivity, which has important implications for understanding Wnt's functional pleiotropy and for developing Wnt-based drugs for cancer and regenerative medicine.
Adams,
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
2010, Pubmed
Adams,
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
2010,
Pubmed
Ahn,
Structural basis of Wnt signaling inhibition by Dickkopf binding to LRP5/6.
2011,
Pubmed
Angers,
Proximal events in Wnt signal transduction.
2009,
Pubmed
Barker,
Mining the Wnt pathway for cancer therapeutics.
2006,
Pubmed
Bazan,
Structural ties between cholesterol transport and morphogen signaling.
2009,
Pubmed
Bhanot,
A new member of the frizzled family from Drosophila functions as a Wingless receptor.
1996,
Pubmed
Bienz,
Biochemistry. A lipid linchpin for Wnt-Fz docking.
2012,
Pubmed
,
Xenbase
Bilic,
Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation.
2007,
Pubmed
Boder,
Yeast surface display for screening combinatorial polypeptide libraries.
1997,
Pubmed
Bourhis,
Reconstitution of a frizzled8.Wnt3a.LRP6 signaling complex reveals multiple Wnt and Dkk1 binding sites on LRP6.
2010,
Pubmed
Carron,
Frizzled receptor dimerization is sufficient to activate the Wnt/beta-catenin pathway.
2003,
Pubmed
,
Xenbase
Chao,
Isolating and engineering human antibodies using yeast surface display.
2006,
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
Chenna,
Multiple sequence alignment with the Clustal series of programs.
2003,
Pubmed
Chien,
A Wnt survival guide: from flies to human disease.
2009,
Pubmed
Cong,
Wnt signals across the plasma membrane to activate the beta-catenin pathway by forming oligomers containing its receptors, Frizzled and LRP.
2004,
Pubmed
Dann,
Insights into Wnt binding and signalling from the structures of two Frizzled cysteine-rich domains.
2001,
Pubmed
,
Xenbase
Emsley,
Features and development of Coot.
2010,
Pubmed
Grumolato,
Canonical and noncanonical Wnts use a common mechanism to activate completely unrelated coreceptors.
2010,
Pubmed
Hausmann,
Wnt lipid modifications: not as saturated as we thought.
2006,
Pubmed
,
Xenbase
He,
LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way.
2004,
Pubmed
Holmen,
A novel set of Wnt-Frizzled fusion proteins identifies receptor components that activate beta -catenin-dependent signaling.
2002,
Pubmed
,
Xenbase
Hsieh,
A new secreted protein that binds to Wnt proteins and inhibits their activities.
1999,
Pubmed
,
Xenbase
Hsieh,
Biochemical characterization of Wnt-frizzled interactions using a soluble, biologically active vertebrate Wnt protein.
1999,
Pubmed
,
Xenbase
Huynh,
Construction of modular and versatile plasmid vectors for the high-level expression of single or multiple genes in insects and insect cell lines.
1999,
Pubmed
Kabsch,
XDS.
2010,
Pubmed
Kawano,
Secreted antagonists of the Wnt signalling pathway.
2003,
Pubmed
,
Xenbase
Kikuchi,
Multiplicity of the interactions of Wnt proteins and their receptors.
2007,
Pubmed
Kim,
Bone regeneration is regulated by wnt signaling.
2007,
Pubmed
Klaus,
Wnt signalling and its impact on development and cancer.
2008,
Pubmed
Krissinel,
Inference of macromolecular assemblies from crystalline state.
2007,
Pubmed
Liepinsh,
NMR structure of the WIF domain of the human Wnt-inhibitory factor-1.
2006,
Pubmed
Logan,
The Wnt signaling pathway in development and disease.
2004,
Pubmed
MacDonald,
Wnt/beta-catenin signaling: components, mechanisms, and diseases.
2009,
Pubmed
,
Xenbase
Malinauskas,
Modular mechanism of Wnt signaling inhibition by Wnt inhibitory factor 1.
2011,
Pubmed
Mao,
Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling.
2002,
Pubmed
Moon,
Wnt/beta-catenin pathway.
2005,
Pubmed
Mulligan,
Secreted Wingless-interacting molecule (Swim) promotes long-range signaling by maintaining Wingless solubility.
2012,
Pubmed
Niehrs,
Function and biological roles of the Dickkopf family of Wnt modulators.
2006,
Pubmed
,
Xenbase
Nusse,
A new nomenclature for int-1 and related genes: the Wnt gene family.
1991,
Pubmed
Nusse,
Wnt genes.
1992,
Pubmed
O'callaghan,
BirA enzyme: production and application in the study of membrane receptor-ligand interactions by site-specific biotinylation.
1999,
Pubmed
Read,
Pushing the boundaries of molecular replacement with maximum likelihood.
2001,
Pubmed
Reya,
Wnt signalling in stem cells and cancer.
2005,
Pubmed
Rice,
Single-wavelength anomalous diffraction phasing revisited.
2000,
Pubmed
Rosenbaum,
The structure and function of G-protein-coupled receptors.
2009,
Pubmed
Semënov,
SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor.
2005,
Pubmed
,
Xenbase
Sheldrick,
A short history of SHELX.
2008,
Pubmed
Smallwood,
Mutational analysis of Norrin-Frizzled4 recognition.
2007,
Pubmed
,
Xenbase
Stroud,
Mechanistic diversity of cytokine receptor signaling across cell membranes.
2004,
Pubmed
Takada,
Monounsaturated fatty acid modification of Wnt protein: its role in Wnt secretion.
2006,
Pubmed
,
Xenbase
Vonrhein,
Automated structure solution with autoSHARP.
2007,
Pubmed
Wang,
Structure-function analysis of Frizzleds.
2006,
Pubmed
Wang,
Wnt7b activates canonical signaling in epithelial and vascular smooth muscle cells through interactions with Fzd1, Fzd10, and LRP5.
2005,
Pubmed
Willert,
Isolation and application of bioactive Wnt proteins.
2008,
Pubmed
Willert,
Wnt proteins are lipid-modified and can act as stem cell growth factors.
2003,
Pubmed
,
Xenbase
