Interaction of Fapp1 with Arf1 and PI4P at a membrane surface: an example of coincidence detection
Yizhou Liu1, Richard A Kahn2, James H Prestegard1
1Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.
Abstract:
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.
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