Single Molecule Diffusion Studies Reveal Rapid Translations Across Target Membrane Surfaces for both p40Phox PX domain and Class III PI3K VPS34 Complex 1, the Autophagy Lipid Kinase

p40Phox PX domain and VPS34 Complex 1 show electrostatic hopping across anionic supported bilayers, producing a higher frequency of long-range displacements than lipid 2-D diffusion.

• Why it matters: Peripheral proteins must rapidly scan membrane surfaces before stable docking, but how electrostatic interactions enable fast search and transition is unclear.
• What they did: Single-molecule tracking on supported lipid bilayers compared LRB-(DO)PE, Rab1A anchored to (DO)PE, the p40Phox PX domain, and VPS34 Complex 1, including tests where bilayer negative charge and substrate lipid (DO)PI(3)P or (DO)PI were present or absent.
• The result: Reduced bilayer negative charge lowered membrane docking for both proteins, and after hopping they entered slower 2-D diffusion; unbinding–hopping–rebinding was not detected with target lipid for PX domain or with substrate lipid for VPS34 Complex 1, but was observed for VPS34 Complex 1 without substrate lipid.

AI summary of the abstract · may contain errors · not medical advice · read the paper.