ALPS

2022-12-08:

ALPS (Amphipathic lipid packing sensor motifs) #

• Identified in 2005.
• 
  • Curving of the plasma Membrane causes lipid packing defects on the side with increased surface area, which is what gets recognized by the ALPS, whereby hydrophobic residues insert between the lipids.
• [The Many Faces of Amphipathic Helices]: Hsp12 is one example; The adsorption of the large AH region of the heat shock protein Hsp12 has a protective effect on the plasma membrane by adjusting its physical properties:
• Amphipathic helices and membrane curvature
  • 
    • (Yellow arrow = increase in hydrophobicity; blue-red arrow = increase in electrostatic interactions/polarity)
    • ALPS (amphipathic lipid packing sensor) motif. It has a cute little table of different ALPSs and their topologies, and α-Synuclein counts as one. They bind to the curved membrane via insertion of hydrophobic molecules.
  • α-Synuclein binds to anionic liposomes in a curvature-dependent manner. Prefers very small liposomes. Displays an affinity for packing defect zones in rigid lipid bilayers, i.e. : α-Synuclein Has a High Affinity for Packing Defects in a Bilayer Membrane: A THERMODYNAMICS STUDY
    • Binding and helix folding of αS depends on the presence of defect structures in the membrane-water interface, which in turn results in lipid ordering in the highly curved vesicular membranes.
    • Surely related to Lewy bodies in Parkinson’s in the vesicles of dopaminergic neurons: Inhibition of mitochondrial fusion by α-synuclein is rescued by PINK1, Parkin and DJ-1
      • Curvature in at least one of the fusing membranes causes stress in the packing of the lipids which is necessary to enable fusion of the leaflets of the two fusing membranes and the formation of a fusion stalk.
    • Yeah, it probably interferes with some stage in exocytosis a la SNARE or whatever.
  • α-Synuclein’s hydrophobic head is ‘stunted’ compared to other AHs as its residues are small and weakly apolar, containing Valine and Alanine.
• Lipids with a large polar head and saturated acyl-chains limit the adsorption of the ALPS motif.L