8ZXD

the Planar Cell Polarity Core Protein Vangl1

Summary for 8ZXD

• Entry DOI: 10.2210/pdb8zxd/pdb
• EMDB information: 60540
• Descriptor: Vang-like protein 1, CHOLESTEROL HEMISUCCINATE, 1,2-DIMYRISTOYL-RAC-GLYCERO-3-PHOSPHOCHOLINE (3 entities in total)
• Functional Keywords: ntd, pcp, vangl, prickle, structural protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 6
• Total formula weight: 370231.63

Authors

Zhang, F.,Chen, S. (deposition date: 2024-06-14, release date: 2024-11-27, Last modification date: 2025-07-23)

Primary citation

Zhang, F.,Li, S.,Wu, H.,Chen, S.
Cryo-EM structure and oligomerization of the human planar cell polarity core protein Vangl1.
Nat Commun, 16:135-135, 2025

PubMed Abstract: Vangl is a planar cell polarity (PCP) core protein essential for aligned cell orientation along the epithelial plane perpendicular to the apical-basal direction, which is important for tissue morphogenesis, development and collective cell behavior. Mutations in Vangl are associated with developmental defects, including neural tube defects (NTDs), according to human cohort studies of sporadic and familial cases. The complex mechanisms underlying Vangl-mediated PCP signaling or Vangl-associated human congenital diseases have been hampered by the lack of molecular characterizations of Vangl. Here, we show biochemical and structural evidence that human Vangl1 oligomerizes as dimers of trimers, and that the dimerization of trimers promotes binding to the PCP effector Prickle1 (Pk1) in vitro. Mapping of human disease-associated point mutations suggests potential pathological mechanisms and paves the way for future studies on the importance of lipid binding, central vestibule and oligomerization of Vangl, thereby providing insights into the molecular mechanisms of the PCP signaling pathway.

PubMed: 39753546
DOI: 10.1038/s41467-024-55397-2

Experimental method

ELECTRON MICROSCOPY (2.9 Å)