7KC4

Human WLS in complex with WNT8A

7KC4 の概要

• エントリーDOI: 10.2210/pdb7kc4/pdb
• EMDBエントリー: 22806
• 分子名称: Protein Wnt-8a, Protein wntless homolog, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: g-protein coupled receptor, palmitoleation, secretion, embryonic development, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 110183.28

構造登録者

Nygaard, R.,Jia, Y.,Kim, J.,Ross, D.,Parisi, G.,Clarke, O.B.,Virshup, D.M.,Mancia, F. (登録日: 2020-10-05, 公開日: 2021-01-06, 最終更新日: 2024-10-09)

主引用文献

Nygaard, R.,Yu, J.,Kim, J.,Ross, D.R.,Parisi, G.,Clarke, O.B.,Virshup, D.M.,Mancia, F.
Structural Basis of WLS/Evi-Mediated Wnt Transport and Secretion.
Cell, 184:194-, 2021

PubMed Abstract: 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.

PubMed: 33357447
DOI: 10.1016/j.cell.2020.11.038

実験手法

ELECTRON MICROSCOPY (3.19 Å)