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TitleStructural Basis of WLS/Evi-Mediated Wnt Transport and Secretion.
Journal, issue, pagesCell, Vol. 184, Issue 1, Page 194-206.e14, Year 2021
Publish dateJan 7, 2021
AuthorsRie Nygaard / Jia Yu / Jonathan Kim / Daniel R Ross / Giacomo Parisi / Oliver B Clarke / David M Virshup / Filippo Mancia /
PubMed AbstractWnts are evolutionarily conserved ligands that signal at short range to regulate morphogenesis, cell fate, and stem cell renewal. The first and essential steps in Wnt secretion are their O- ...Wnts are evolutionarily conserved ligands that signal at short range to regulate morphogenesis, cell fate, and stem cell renewal. The first and essential steps in Wnt secretion are their O-palmitoleation and subsequent loading onto the dedicated transporter Wntless/evenness interrupted (WLS/Evi). We report the 3.2 Å resolution cryogenic electron microscopy (cryo-EM) structure of palmitoleated human WNT8A in complex with WLS. This is accompanied by biochemical experiments to probe the physiological implications of the observed association. The WLS membrane domain has close structural homology to G protein-coupled receptors (GPCRs). A Wnt hairpin inserts into a conserved hydrophobic cavity in the GPCR-like domain, and the palmitoleate protrudes between two helices into the bilayer. A conformational switch of highly conserved residues on a separate Wnt hairpin might contribute to its transfer to receiving cells. This work provides molecular-level insights into a central mechanism in animal body plan development and stem cell biology.
External linksCell / PubMed:33357447 / PubMed Central
MethodsEM (single particle)
Resolution3.19 Å
Structure data

22806

7kc4

EMDB-22806, PDB-7kc4:
Human WLS in complex with WNT8A
Method: EM (single particle) / Resolution: 3.19 Å

Chemicals

ChemComp-PLM:
PALMITIC ACID / Palmitic acid

ChemComp-DR9:
1-CIS-9-OCTADECANOYL-2-CIS-9-HEXADECANOYL PHOSPHATIDYL GLYCEROL

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / G-protein coupled receptor / palmitoleation / secretion / embryonic development

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