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FYVE domain

Class: Phospholipid Binding

Brief description: FYVE domains are approximately 70-80 residues in length and contain 8 Cys or 7 Cys and 1 His. They coordinate two Zn2+ ions. They are highly similar to FYVE domains and are the latest addition to the family of membrane targeting family of proteins. They are activly involed in endosomal localization of proteins important for membrane-trafficking in yeast and mammals. They also participate in cyteoskeleton regulation and receptor signaling. The discovery that effectors of class III PI3-kinases are localized by binding PI3P via their FYVE domains escalated the interest in these domains. They specifically bind PtdIns(3)P in vitro.

Structure:

structure Crystal structure of the Vps27p FYVE domains showed a compact core comprising of two small double stranded beta-sheets and a C-terminal alpha-helix. It also revealed a shallow pocket that binds PI3P. The Zn2+-coordinating Cys/His pairs are located such that the first and their pairs bind one Zinc atom while second and fourth pair coordinate another. Surface of the Vsp27p-FYVE domain contains a basic region due to a conserved RKHHCR motif. Mutation in this motif disrupts the PI3P-binding. It has been proposed that FYVE domains bind the membrane in a manner that woul facilitate binding of PI3P to the pocket and interfacial penetration of Leu residues in an exposed loop.

Subcellular Localization:

Only a few FYVE domains (e.g., those of endofin, FENS-1, and SARA) are autonomously targeted to endosomal membranes upon ectopical expression in the cell. Tandem fusion construct of the FYVE domains of Hrs readily translocates to endosomes. Dimerization of the frabin FYVE domain causes its endosomal localization. Minor structural variations in the turret loop of the FYVE domain have been shown to cause subcellular localization behaviors of the endofin and FENS-1 FYVE domains.

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Relevant Literature

1. Kutateladze, T.G., Ogburn, K.D., Watson, W.T., de Beer, T., Emr, S.D., Burd, C.G. and Overduin, M. (1999) Phosphatidylinositol 3-phosphate recognition by the FYVE domain. Mol Cell, 3, 805-811.

2. Kutateladze, T.G. (2006) Phosphatidylinositol 3-phosphate recognition and membrane docking by the FYVE domain. Biochim Biophys Acta, 1761, 868-877.

3. Kutateladze, T. and Overduin, M. (2001) Structural mechanism of endosome docking by the FYVE domain. Science, 291, 1793-1796.

4. Cho, W. and Stahelin, R.V. (2005) Membrane-protein interactions in cell signaling and membrane trafficking. Annu Rev Biophys Biomol Struct, 34, 119-151.