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Chem Phys Lipids. 2014 Sep;182:3-18. doi: 10.1016/j.chemphyslip.2014.02.002. Epub 2014 Feb 17.

Cellular and molecular interactions of phosphoinositides and peripheral proteins.

Author information

1
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine-South Bend, South Bend, IN 46617, United States; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, United States; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, United States. Electronic address: rstaheli@iupui.edu.
2
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, United States; Mike and Josie Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, United States.
3
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, United States.

Abstract

Anionic lipids act as signals for the recruitment of proteins containing cationic clusters to biological membranes. A family of anionic lipids known as the phosphoinositides (PIPs) are low in abundance, yet play a critical role in recruitment of peripheral proteins to the membrane interface. PIPs are mono-, bis-, or trisphosphorylated derivatives of phosphatidylinositol (PI) yielding seven species with different structure and anionic charge. The differential spatial distribution and temporal appearance of PIPs is key to their role in communicating information to target proteins. Selective recognition of PIPs came into play with the discovery that the substrate of protein kinase C termed pleckstrin possessed the first PIP binding region termed the pleckstrin homology (PH) domain. Since the discovery of the PH domain, more than ten PIP binding domains have been identified including PH, ENTH, FYVE, PX, and C2 domains. Representative examples of each of these domains have been thoroughly characterized to understand how they coordinate PIP headgroups in membranes, translocate to specific membrane docking sites in the cell, and function to regulate the activity of their full-length proteins. In addition, a number of novel mechanisms of PIP-mediated membrane association have emerged, such as coincidence detection-specificity for two distinct lipid headgroups. Other PIP-binding domains may also harbor selectivity for a membrane physical property such as charge or membrane curvature. This review summarizes the current understanding of the cellular distribution of PIPs and their molecular interaction with peripheral proteins.

KEYWORDS:

C2 domain; FYVE domain; Lipid binding; Membrane binding; PH domain; PI(3)P; PI(3,4,5)P(3); PI(4,5)P(2); Peripheral protein.; Phosphoinsoitide

PMID:
24556335
PMCID:
PMC4484752
DOI:
10.1016/j.chemphyslip.2014.02.002
[Indexed for MEDLINE]
Free PMC Article
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