8TZS

Structure of human WLS

8TZS の概要

• エントリーDOI: 10.2210/pdb8tzs/pdb
• EMDBエントリー: 41768
• 分子名称: Protein wntless homolog (1 entity in total)
• 機能のキーワード: membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 62317.97

構造登録者

Qi, X.,Hu, Q.,Li, X. (登録日: 2023-08-27, 公開日: 2023-10-18, 最終更新日: 2025-06-04)

主引用文献

Qi, X.,Hu, Q.,Elghobashi-Meinhardt, N.,Long, T.,Chen, H.,Li, X.
Molecular basis of Wnt biogenesis, secretion, and Wnt7-specific signaling.
Cell, 186:5028-5040.e14, 2023

PubMed Abstract: Wnt proteins are enzymatically lipidated by Porcupine (PORCN) in the ER and bind to Wntless (WLS) for intracellular transport and secretion. Mechanisms governing the transfer of these low-solubility Wnts from the ER to the extracellular space remain unclear. Through structural and functional analyses of Wnt7a, a crucial Wnt involved in central nervous system angiogenesis and blood-brain barrier maintenance, we have elucidated the principles of Wnt biogenesis and Wnt7-specific signaling. The Wnt7a-WLS complex binds to calreticulin (CALR), revealing that CALR functions as a chaperone to facilitate Wnt transfer from PORCN to WLS during Wnt biogenesis. Our structures, functional analyses, and molecular dynamics simulations demonstrate that a phospholipid in the core of Wnt-bound WLS regulates the association and dissociation between Wnt and WLS, suggesting a lipid-mediated Wnt secretion mechanism. Finally, the structure of Wnt7a bound to RECK, a cell-surface Wnt7 co-receptor, reveals how RECK engages the N-terminal domain of Wnt7a to activate Wnt7-specific signaling.

PubMed: 37852257
DOI: 10.1016/j.cell.2023.09.021

実験手法

ELECTRON MICROSCOPY (3.84 Å)