EMD-41767

Single-particle
3.5 Å
EMD-41767 Deposition: 27/08/2023
Map released: 18/10/2023
Last modified: 30/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-41767

Structure of human Wnt3a bound to WLS and CALR

EMD-41767

Single-particle
3.5 Å
EMD-41767 Deposition: 27/08/2023
Map released: 18/10/2023
Last modified: 30/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens
Sample: Wnt3a-WLS-CALR Complex
Fitted models: 8tzr (Avg. Q-score: 0.381)

Deposition Authors: Qi X, Hu Q, Li X
Molecular basis of Wnt biogenesis, secretion, and Wnt7-specific signaling.
Qi X, Hu Q, Elghobashi-Meinhardt N , Long T, Chen H , Li X
(2023) Cell , 186 , 5028 - 5040.e14
PUBMED: 37852257
DOI: doi:10.1016/j.cell.2023.09.021
ISSN: 1097-4172
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 RECKCC4 engages the N-terminal domain of Wnt7a to activate Wnt7-specific signaling.