Interaction of Fapp1 with Arf1 and PI4P at a membrane surface: an example of coincidence detection.
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.
Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.
Yizhou
Y
Liu
Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: rkahn@emory.edu.
Richard A
RA
Kahn
Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA. Electronic address: jpresteg@ccrc.uga.edu.
James H
JH
Prestegard
D020823:ADP-Ribosylation Factor 1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D011487:Protein Conformation
D048868:Adaptor Proteins, Signal Transducing; C487037:PLEKHA3 protein, human; D018129:Phosphatidylinositol Phosphates; C037178:phosphatidylinositol 4-phosphate; D020823:ADP-Ribosylation Factor 1