Structural basis for the interaction between the cell polarity proteins Par3 and Par6

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Cell polarity is fundamental for cell function and development.
• The Par protein complex (aPKC, Par3, Par6) regulates asymmetric protein localization.
• Dysfunction of the Par complex is linked to developmental abnormalities and cancer.

Purpose of the Study:

• To investigate the interaction between Par3 and Par6.
• To elucidate the role of a specific motif in Par6 for Par3 binding and localization.
• To understand the structural basis of Par3-Par6 complex formation.

Main Methods:

• In vitro binding assays.
• Cell-based localization studies in cultured cells.
• Structural analyses using X-ray crystallography and NMR spectroscopy.
• Functional studies in fly embryos.

Main Results:

• A PDZ domain-binding motif in Par6 was identified, crucial for Par3 interaction and membrane localization.
• The motif was functionally redundant with Par3's PDZ domain in targeting Par6 to the cell cortex in vivo.
• Structural analysis revealed that Par3's PDZ1 and PDZ3 domains bind to the Par6 motif, enabling simultaneous Par6 recruitment.

Conclusions:

• Par3 can bind two Par6 proteins simultaneously via its PDZ1 and PDZ3 domains.
• This multivalent interaction facilitates the assembly of polarity protein networks.
• Understanding these interactions provides insights into cell polarity regulation and disease mechanisms.