title: Phosphatidylinositol 3-phosphate recognition and membrane docking by the FYVE domain.
abstract: The FYVE domain is a small zinc binding module that recognizes phosphatidylinositol 3-phosphate [PtdIns(3)P], a phospholipid enriched in membranes of early endosomes and other endocytic vesicles. It is usually present as a single module or rarely as a tandem repeat in eukaryotic proteins involved in a variety of biological processes including endo- and exocytosis, membrane trafficking and phosphoinositide metabolism. A number of FYVE domain-containing proteins are recruited to endocytic membranes through the specific interaction of their FYVE domains with PtdIns(3)P. Structures and PtdIns(3)P binding modes of several FYVE domains have recently been characterized, shedding light on the molecular basis underlying multiple cellular functions of these proteins. Here, structural and functional aspects and the current mechanism of the multivalent membrane anchoring by monomeric or dimeric FYVE domain are reviewed. This mechanism involves stereospecific recognition of PtdIns(3)P that is facilitated by non-specific electrostatic contacts and modulated by the histidine switch, and is accompanied by hydrophobic insertion. Contributions of each component to the FYVE domain specificity and affinity for PtdIns(3)P-containing membranes are discussed.
authors.affiliation: Department of Pharmacology, University of Colorado Health Sciences Center, 12801 East 17th Avenue, Aurora, CO 80045, USA. tatiana.kutateladze@uchsc.edu
authors.forename: Tatiana G
authors.initials: TG
authors.lastname: Kutateladze
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D006639:Histidine / Q000737:chemistry; D006801:Humans; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018129:Phosphatidylinositol Phosphates / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012680:Sensitivity and Specificity; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
chemical_list: D008563:Membrane Lipids; D018129:Phosphatidylinositol Phosphates; C055525:phosphatidylinositol 3-phosphate; D006639:Histidine