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TitleStructural basis of human VANGL-PRICKLE interaction.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 132, Year 2025
Publish dateJan 3, 2025
AuthorsYanyi Song / Shuyi Jian / Junlin Teng / Pengli Zheng / Zhe Zhang /
PubMed AbstractPlanar cell polarity (PCP) is an evolutionarily conserved process for development and morphogenesis in metazoans. The well-organized polarity pattern in cells is established by the asymmetric ...Planar cell polarity (PCP) is an evolutionarily conserved process for development and morphogenesis in metazoans. The well-organized polarity pattern in cells is established by the asymmetric distribution of two core protein complexes on opposite sides of the cell membrane. The Van Gogh-like (VANGL)-PRICKLE (PK) pair is one of these two key regulators; however, their structural information and detailed functions have been unclear. Here, we present five cryo-electron microscopy structures of human VANGL1, VANGL2, and their complexes with PK1 at resolutions of 2.2-3.0 Å. Through biochemical and cell imaging experiments, we decipher the molecular details of the VANGL-PK interaction. Furthermore, we reveal that PK1 can target VANGL-containing intracellular vesicles to the peripheral cell membrane. These findings provide a solid foundation to understand the explicit interaction between VANGL and PK while opening new avenues for subsequent studies of the PCP pathway.
External linksNat Commun / PubMed:39753555 / PubMed Central
MethodsEM (single particle)
Resolution2.2 - 3.0 Å
Structure data

61545

9jk6

EMDB-61545, PDB-9jk6:
Human VANGL1 hexamer
Method: EM (single particle) / Resolution: 3.0 Å

61546

9jk7

EMDB-61546, PDB-9jk7:
Human VANGL2 hexamer
Method: EM (single particle) / Resolution: 2.9 Å

61547

9jk8

EMDB-61547, PDB-9jk8:
Human VANGL1 in complex with PK1
Method: EM (single particle) / Resolution: 2.6 Å

61548

9jk9

EMDB-61548, PDB-9jk9:
Human VANGL1 in complex with a PK1 peptide (residues 745-790)
Method: EM (single particle) / Resolution: 2.2 Å

61549

9jka

EMDB-61549, PDB-9jka:
Human VANGL2 in complex with a PK1 peptide (residues 745-790)
Method: EM (single particle) / Resolution: 2.5 Å

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / VANGL / Planar cell polarity / PCP / Prickle1

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