Phospholipases and Membrane Curvature: What Is Happening at the Surface?

In this revision work, we emphasize the close relationship between the action of phospholipases and the modulation of membrane curvature and curvature stress resulting from this activity. The alteration of the tridimensional structure of membranes upon the action of phospholipases is analyzed based on studies on model lipid membranes. The transient unbalance of both compositional and physical membrane properties between the hemilayers upon phospholipase activity lead to curvature tension and the catalysis of several membrane-related processes.

The influence of myristoylation, liposome surface charge and nucleic acid interaction in the partition properties of HIV-1 Gag-N-terminal peptides to membranes.

The group-specific antigen (GAG) polyprotein of HIV-1 is the main coordinator of the virus assembly process at the plasma membrane (PM) and is directed by its N-terminal matrix domain (MA). MA is myristoylated and possess a highly basic region (HBR) responsible for the interaction with the negative lipids of the PM, especially with PIP. In addition, MA binds RNA molecules proposed as a regulatory step of the assembly process.

Miltefosine inhibits the membrane remodeling caused by phospholipase action by changing membrane physical properties.

Miltefosine (hexadecylphosphocholine or HePC) is an alkylphosphocholine approved for the treatment of visceral and cutaneous Leishmaniasis. HePC exerts its effect by interacting with lipid membranes and affecting membrane-dependent processes. The molecular geometry of HePC suggests that the pharmacological function of HePC is to alter membrane curvature.

Detecting phospholipase activity with the amphipathic lipid packing sensor motif of ArfGAP1.

The amphipathic lipid packing sensor (ALPS) motif of ArfGAP1 brings this GTPase activating protein to membranes of high curvature. Phospholipases are phospholipid-hydrolyzing enzymes that generate different lipid products that alter the lateral organization of membranes. Here, we evaluate by fluorescence microscopy how in-situ changes of membrane lipid composition driven by the activity of different phospholipases promotes the binding of ALPS.