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Science 291 (5509): 1793-1796

Copyright © 2001 by the American Association for the Advancement of Science

Structural Mechanism of Endosome Docking by the FYVE Domain

Tatiana Kutateladze,* Michael Overduin

The recruitment of trafficking and signaling proteins to membranes containing phosphatidylinositol 3-phosphate [PtdIns(3)P] is mediated by FYVE domains. Here, the solution structure of the FYVE domain of the early endosome antigen 1 protein (EEA1) in the free state was compared with the structures of the domain complexed with PtdIns(3)P and mixed micelles. The multistep binding mechanism involved nonspecific insertion of a hydrophobic loop into the lipid bilayer, positioning and activating the binding pocket. Ligation of PtdIns(3)P then induced a global structural change, drawing the protein termini over the bound phosphoinositide by extension of a hinge. Specific recognition of the 3-phosphate was determined indirectly and directly by two clusters of conserved arginines.

Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
*   To whom correspondence should be addressed. E-mail: tatiana.kutateladze{at}

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   Abstract »    Full Text »    PDF »
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Phosphatidylinositol 3-Phosphate Induces the Membrane Penetration of the FYVE Domains of Vps27p and Hrs.
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J. Biol. Chem. 277, 26379-26388
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Functional Dissection of Lipid and Protein Kinase Signals of PIKfyve Reveals the Role of PtdIns 3,5-P2 Production for Endomembrane Integrity.
O. C. Ikonomov, D. Sbrissa, K. Mlak, M. Kanzaki, J. Pessin, and A. Shisheva (2002)
J. Biol. Chem. 277, 9206-9211
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Phosphatidylinositol 3-Phosphate-interacting Domains in PIKfyve. BINDING SPECIFICITY AND ROLE IN PIKfyve ENDOMEMBRANE LOCALIZATION.
D. Sbrissa, O. C. Ikonomov, and A. Shisheva (2002)
J. Biol. Chem. 277, 6073-6079
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The C Terminus of the Vps34p Phosphoinositide 3-Kinase Is Necessary and Sufficient for the Interaction with the Vps15p Protein Kinase.
Y. V. Budovskaya, H. Hama, D. B. DeWald, and P. K. Herman (2002)
J. Biol. Chem. 277, 287-294
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Location, Location, Location: Membrane Targeting Directed by PX Domains.
T. K. Sato, M. Overduin, and S. D. Emr (2001)
Science 294, 1881-1885
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J. Biol. Chem. 276, 45868-45875
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Role of the FYVE Finger and the RUN Domain for the Subcellular Localization of Rabip4.
M. Mari, E. Macia, Y. Le Marchand-Brustel, and M. Cormont (2001)
J. Biol. Chem. 276, 42501-42508
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FYVE Domain Targets Pib1p Ubiquitin Ligase to Endosome and Vacuolar Membranes.
M. E. Shin, K. D. Ogburn, O. A. Varban, P. M. Gilbert, and C. G. Burd (2001)
J. Biol. Chem. 276, 41388-41393
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Agonist-dependent Traffic of Raft-associated Ras and Raf-1 Is Required for Activation of the Mitogen-activated Protein Kinase Cascade.
M. A. Rizzo, C. A. Kraft, S. C. Watkins, E. S. Levitan, and G. Romero (2001)
J. Biol. Chem. 276, 34928-34933
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