Gβγ engages PLCβ3 at multiple sites to reorient and facilitate its activation.

Gβ3γ3 acts as a critical positive allosteric modulator, reorienting PLCβ3 to enhance activation and PI(4,5)P2 hydrolysis at the plasma membrane.

• Why it matters: Understanding Gβ3γ3’s role in PLCβ3 activation fills a knowledge gap about G protein subunit interactions and regulation mechanisms, which are vital for cellular signaling.
• What they did: The study used cryo-electron microscopy, functional assays, and bioluminescence resonance energy transfer to analyze Gβ3γ3’s binding to PLCβ3 and its cooperative role with Gαq in activating the enzyme.
• The result: Findings show Gβ3γ3 binds multiple sites on PLCβ3, facilitating its reorientation and maximal activity, thereby enabling efficient downstream calcium signaling and cellular responses.