Lipid modification in Wnt structure and function.
OBJECTIVE
Wnt proteins are morphogens encoded by 19 mammalian genes that play essential roles in embryonic development, stem cell renewal, and adult tissue homeostasis. The recent publication of the first crystal structure of a Wnt protein represents a key step in the study of Wnt signaling.


RESULTS
We discuss the basic aspects of Wnt signaling, provide historical background for why the proteins have been so challenging to study from a biochemical perspective, describe the lipid modifications that occur to Wnt proteins, and then discuss the implications of the recently reported crystal structure.


CONCLUSIONS
The recent determination of the Wnt8-Fz8 structure has created new opportunities to better understand the mechanisms by which Wnt proteins activate downstream signaling pathways and has further clarified why lipid modification of Wnt is required for activation.
Laboratory of Structural Studies, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
Jiyuan
J
Ke
H Eric
HE
Xu
Bart O
BO
Williams
D000818:Animals; D004330:Drosophila / Q000737:chemistry / Q000235:genetics; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics; D051157:Frizzled Receptors / Q000737:chemistry* / Q000235:genetics; D006031:Glycosylation; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008055:Lipids / Q000737:chemistry*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000235:genetics; D013329:Structure-Activity Relationship; D051153:Wnt Proteins / Q000737:chemistry* / Q000235:genetics; D060449:Wnt Signaling Pathway
D029721:Drosophila Proteins; D051157:Frizzled Receptors; D008024:Ligands; D008055:Lipids; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; C491438:Wnt5 protein, Drosophila; C058784:fz protein, Drosophila