: / : / Wnt protein secretion / neural crest cell fate commitment / positive regulation of Wnt protein secretion / WNT ligand biogenesis and trafficking / secondary palate development / cementum mineralization / beta-catenin destruction complex disassembly / hindbrain development ...: / : / Wnt protein secretion / neural crest cell fate commitment / positive regulation of Wnt protein secretion / WNT ligand biogenesis and trafficking / secondary palate development / cementum mineralization / beta-catenin destruction complex disassembly / hindbrain development / Wnt-protein binding / exocrine pancreas development / frizzled binding / Class B/2 (Secretin family receptors) / Disassembly of the destruction complex and recruitment of AXIN to the membrane / anterior/posterior axis specification / midbrain development / organelle membrane / cell fate commitment / mesoderm formation / positive regulation of Wnt signaling pathway / canonical Wnt signaling pathway / endomembrane system / response to retinoic acid / TCF dependent signaling in response to WNT / cytokine activity / intracellular protein transport / trans-Golgi network / neuron differentiation / Wnt signaling pathway / positive regulation of canonical Wnt signaling pathway / endocytic vesicle membrane / early endosome membrane / positive regulation of canonical NF-kappaB signal transduction / cytoplasmic vesicle / collagen-containing extracellular matrix / early endosome / receptor ligand activity / Golgi membrane / endoplasmic reticulum membrane / Golgi apparatus / endoplasmic reticulum / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular exosome / extracellular region / identical protein binding / plasma membrane / cytosol 類似検索 - 分子機能
Wnt-8 protein / Protein Wnt-8A/8C / Protein wntless / : / Wntless-like, transmembrane domain / Wnt protein, conserved site / Wnt-1 family signature. / Wnt / Wnt, C-terminal domain / wnt family / found in Wnt-1 類似検索 - ドメイン・相同性
Protein wntless homolog / Protein Wnt-8a 類似検索 - 構成要素
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R35 GM132120
米国
National Research Foundation (NRF, Singapore)
MOH-000155
シンガポール
引用
ジャーナル: Cell / 年: 2021 タイトル: Structural Basis of WLS/Evi-Mediated Wnt Transport and Secretion. 著者: Rie Nygaard / Jia Yu / Jonathan Kim / Daniel R Ross / Giacomo Parisi / Oliver B Clarke / David M Virshup / Filippo Mancia / 要旨: 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- ...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.
EMPIAR-10699 (タイトル: Human WLS in complex with WNT8A / Data size: 1.9 TB Data #1: Unaligned multi frame micrographs of WNT8A WLS complex [micrographs - multiframe])