Pleckstrin homology (PH) domains and phosphoinositides
- 1 December 2007
- journal article
- Published by Portland Press Ltd. in Biochemical Society Symposium
- Vol. 74 (1), 81-93
- https://doi.org/10.1042/bss0740081
Abstract
PH (pleckstrin homology) domains represent the 11th most common domain in the human proteome. They are best known for their ability to bind phosphoinositides with high affinity and specificity, although it is now clear that less than 10% of all PH domains share this property. Cases in which PH domains bind specific phosphoinositides with high affinity are restricted to those phosphoinositides that have a pair of adjacent phosphates in their inositol headgroup. Those that do not [PtdIns3P, PtdIns5P and PtdIns(3,5)P2] are instead recognized by distinct classes of domains including FYVE domains, PX (phox homology) domains, PHD (plant homeodomain) fingers and the recently identified PROPPINs (b-propellers that bind polyphosphoinositides). Of the 90% of PH domains that do not bind strongly and specifically to phosphoinositides, few are well understood. One group of PH domains appears to bind both phosphoinositides (with little specificity) and Arf (ADP-ribosylation factor) family small G-proteins, and are targeted to the Golgi apparatus where both phosphoinositides and the relevant Arfs are both present. Here, the PH domains may function as coincidence detectors. A central challenge in understanding the majority of PH domains is to establish whether the very low affinity phosphoinositide binding reported in many cases has any functional relevance. For PH domains from dynamin and from Dbl family proteins, this weak binding does appear to be functionally important, although its precise mechanistic role is unclear. In many other cases, it is quite likely that alternative binding partners are more relevant, and that the observed PH domain homology represents conservation of structural fold rather than function.Keywords
This publication has 81 references indexed in Scilit:
- The Arabidopsis homolog of trithorax, ATX1, binds phosphatidylinositol 5-phosphate, and the two regulate a common set of target genesProceedings of the National Academy of Sciences of the United States of America, 2006
- Multiple Pools of Phosphatidylinositol 4-Phosphate Detected Using the Pleckstrin Homology Domain of Osh2pOnline Journal of Public Health Informatics, 2004
- Ent5p Is Required with Ent3p and Vps27p for Ubiquitin-dependent Protein Sorting into the Multivesicular BodyMolecular Biology of the Cell, 2004
- Ent3p Is a PtdIns(3,5)P2 Effector Required for Protein Sorting to the Multivesicular BodyDevelopmental Cell, 2003
- Phosphatidylinositol 3-Phosphate Induces the Membrane Penetration of the FYVE Domains of Vps27p and HrsOnline Journal of Public Health Informatics, 2002
- Multivalent Endosome Targeting by Homodimeric EEA1Molecular Cell, 2001
- Structural Mechanism of Endosome Docking by the FYVE DomainScience, 2001
- Localization of phosphatidylinositol 3-phosphate in yeast and mammalian cellsThe EMBO Journal, 2000
- Structure of the Enabled/VASP Homology 1 Domain–Peptide Complex: A Key Component in the Spatial Control of Actin AssemblyCell, 1999
- Identification of the Binding Site for Acidic Phospholipids on the PH Domain of Dynamin: Implications for Stimulation of GTPase ActivityJournal of Molecular Biology, 1996