Structural basis of wedging the Golgi membrane by FAPP pleckstrin homology domains

EMBO Rep. 2010 Apr;11(4):279-84. doi: 10.1038/embor.2010.28. Epub 2010 Mar 19.

Abstract

The mechanisms underlying Golgi targeting and vesiculation are unknown, although the responsible phosphatidylinositol 4-phosphate (PtdIns(4)P) ligand and four-phosphate-adaptor protein (FAPP) modules have been defined. The micelle-bound structure of the FAPP1 pleckstrin homology domain reveals how its prominent wedge independently tubulates Golgi membranes by leaflet penetration. Mutations compromising the exposed hydrophobicity of full-length FAPP2 abolish lipid monolayer binding and compression. The trafficking process begins with an electrostatic approach, phosphoinositide sampling and perpendicular penetration. Extensive protein contacts with PtdIns(4)P and neighbouring phospholipids reshape the bilayer and initiate tubulation through a conserved wedge with features shared by diverse protein modules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry*
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Golgi Apparatus / chemistry
  • Golgi Apparatus / metabolism*
  • Humans
  • Micelles
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Phosphatidylinositol Phosphates / metabolism
  • Protein Binding / genetics
  • Protein Binding / physiology
  • Protein Structure, Secondary
  • Protein Structure, Tertiary / genetics
  • Protein Structure, Tertiary / physiology

Substances

  • Adaptor Proteins, Signal Transducing
  • Micelles
  • PLEKHA3 protein, human
  • Phosphatidylinositol Phosphates
  • phosphatidylinositol 4-phosphate