Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2010 Jul;6(7):507-13.
doi: 10.1038/nchembio.390.

Translation of the phosphoinositide code by PI effectors

Tatiana G Kutateladze  1
Affiliations
Review

Translation of the phosphoinositide code by PI effectors

Tatiana G Kutateladze. Nat Chem Biol. 2010 Jul.

Abstract

Phosphoinositide (PI) lipids are essential components of eukaryotic cell membranes. They are produced by mono-, bis- and trisphosphorylation of the inositol headgroup of phosphatidylinositol (PtdIns) and are concentrated in separate pools of cytosolic membranes. PIs serve as markers of the cell compartments and form unique docking sites for protein effectors. Collectively, seven known PIs, the protein effectors that bind them and enzymes that generate or modify PIs compose a remarkably complex protein-lipid signaling network. A number of cytosolic proteins contain one or several effector modules capable of recognizing individual PIs and recruiting the host proteins to distinct intracellular compartment. The recently determined atomic-resolution structures and membrane-targeting mechanisms of a dozen PI effectors have provided insights into the molecular basis for regulation of endocytic membrane trafficking and signaling. In this review, I highlight the structural aspects of the deciphering of the 'PI code' by the most common PI-recognizing effectors and discuss the mechanistic details of their membrane anchoring.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Subcellular localization of Pls
PIs are concentrated in distinct pools of cytosolic membranes and serve as markers of various cell compartments and regions. Only predominant PIs are shown for simplicity. A heterogeneous distribution of PIs within a given membrane has also been observed. EE, early endosome; MVB, multivesicular bodies; PI3P, PtdIns(3)P; PI4P, PtdIns(4)P; PI(3,4)P2, PtdIns(3,4)P2; PI(3,5)P2, PtdIns(3,5)P2; PI(4,5)P2, PtdIns(4,5)P2; PI(3,4,5)P3; PtdIns(3,4,5)P3.
Figure 2
Figure 2. PI-recognizing effectors
Signaling domains and their target PIs are colored as in Figure 1, according to their predominant distribution in intracellular membranes. PI3P, PtdIns(3)P; PI4P, PtdIns(4)P; PI5P, PtdIns(5)P; PI(3,4)P2, PtdIns(3,4)P2; PI(3,5)P2, PtdIns(3,5)P2; PI(4,5)P2, PtdIns(4,5)P2; PI(3,4,5)P3; PtdIns(3,4,5)P3.
Figure 3
Figure 3. Molecular mechanism of PI recognition
(a–c) Crystal structures of (a) the EEA1 FYVE domain in complex with inositol 1,3-bisphosphate (Ins(1,3)P2), a headgroup of PtdIns(3)P (1JOC), (b) the Grp1 PH domain in complex with inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4), a headgroup of PtdIns(3,4,5)P3 (1FGY) and (c) the p40phox PX domain in complex with dibutanoyl PtdIns(3)P (PI3P) (1H6H).
Figure 4
Figure 4. The structural basis for deciphering the PI code
(a–e) Schematic diagrams showing PtdIns(3)P headgroup coordination by (a) EEA1 FYVE (1JOC) and (c) p40phox PX (1H6H) domains; PtdIns(3,4,5)P3 headgroup coordination by (b) Grp1 PH domain (1FGY); and PtdIns(4,5)P2 headgroup coordination by (d) CALM ANTH (1HFA) and (e) Epsin1 ENTH (1H0A) domains. Only charged residues of the proteins are depicted for clarity.
See this image and copyright information in PMC

References

    1. Lemmon MA. Membrane recognition by phospholipid-binding domains. Nat. Rev. Mol. Cell Biol. 2008;9:99–111. - PubMed
    1. Hurley JH. Membrane binding domains. Biochim Biophys Acta. 2006;1761:805–811. - PMC - PubMed
    1. Di Paolo G, De Camilli P. Phosphoinositides in cell regulation and membrane dynamics. Nature. 2006;443:651–657. - PubMed
    1. Roth MG. Phosphoinositides in constitutive membrane traffic. Physiol. Rev. 2004;84:699–730. - PubMed
    1. Vanhaesebroeck B, et al. Synthesis and function of 3-phosphorylated inositol lipids. Annu. Rev. Biochem. 2001;70:535–602. - PubMed

Publication types

MeSH terms

Substances