Inositol-lipid binding motifs: signal integrators through protein-lipid and protein-protein interactions.
Inositol lipids have emerged as universal lipid regulators of protein signaling complexes in defined membrane compartments. The number of protein modules that are known to recognise these membrane lipids is rapidly increasing. Pleckstrin homology domains, FYVE domains, PX domains, ENTH domains, CALM domains, PDZ domains, PTB domains and FERM domains are all inositide-recognition modules. The latest additions to this list are members of the clathrin adaptor protein and arrestin families. Initially, inositol lipids were believed to recruit signaling molecules to specific membrane compartments, but many of the domains clearly do not possess high enough affinity to act alone as localisation signals. Another important notion is that some (and probably most) of these protein modules also have protein binding partners, and their protein- and lipid-binding activities might influence one another through allosteric mechanisms. Comparison of the structural features of these domains not only reveals a high degree of conservation of their lipid interaction sites but also highlights their evolutionary link to protein modules known for protein-protein interactions. Protein-protein interactions involving lipid-binding domains could serve as the basis for phosphoinositide-induced conformational regulation of target proteins at biological membranes. Therefore, these modules function as crucially important signal integrators, which explains their involvement in a broad range of regulatory functions in eukaryotic cells.
Balla
Tamas
T
Endocrinology and Reproduction Research Branch, NICHD, National Institutes of Health, Bethesda, MD 20892, USA. ballat@mail.nih.gov
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D020816:Amino Acid Motifs; D002462:Cell Membrane / Q000378:metabolism; D007294:Inositol / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism*; D008958:Models, Molecular; D010716:Phosphatidylinositols / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D008563:Membrane Lipids; D010716:Phosphatidylinositols; D007294:Inositol