Interaction of Fapp1 with Arf1 and PI4P at a membrane surface: an example of coincidence detection

Structure. 2014 Mar 4;22(3):421-30. doi: 10.1016/j.str.2013.12.011. Epub 2014 Jan 23.


Interactions among ADP-ribosylation factors (ARFs), various adaptor proteins, and membrane lipids are essential for intracellular vesicle transport of a variety of cellular materials. Here, we present nuclear magnetic resonance (NMR)-based information on the nature of the interaction of yeast Arf1 (yArf1) and the pleckstrin homology (PH) domain of four-phosphate-adaptor protein 1 (Fapp1) as it occurs at a model membrane surface. Interactions favor a model in which Fapp1 is partially embedded in the membrane and interacts with a membrane-associated Arf1 molecule primarily through contacts between residues in switch I of Arf1 and regions near and under the solution exposed C-terminal extension of the PH domain. The Arf1 binding site on Fapp1-PH is distinct from a positively charged phosphatidylinositol-4-phosphate (PI4P) binding site. A structural model is constructed that supports coincidence detection of both activated ARF and PI4P as a mechanism facilitating Fapp1 recruitment to membranes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ADP-Ribosylation Factor 1 / chemistry*
  • ADP-Ribosylation Factor 1 / genetics
  • ADP-Ribosylation Factor 1 / metabolism*
  • Adaptor Proteins, Signal Transducing / chemistry*
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Binding Sites
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Humans
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Phosphatidylinositol Phosphates / metabolism
  • Protein Conformation


  • Adaptor Proteins, Signal Transducing
  • PLEKHA3 protein, human
  • Phosphatidylinositol Phosphates
  • phosphatidylinositol 4-phosphate
  • ADP-Ribosylation Factor 1