Lipid binding domains: more than simple lipid effectors

Abstract

The spatial and temporal regulation of lipid molecules in cell membranes is a hallmark of cellular signaling and membrane trafficking events. Lipid-mediated targeting provides for strict control and versatility, because cell membranes harbor a large number of lipid molecules with variation in head group and acyl chain structures. Signaling and trafficking proteins contain a large number of modular domains that exhibit specific lipid binding properties and play a critical role in their localization and function. Nearly 20 years of research including structural, computational, biochemical and biophysical studies have demonstrated how these lipid-binding domains recognize their target lipid and achieve subcellular localization. The integration of this individual lipid-binding domain data in the context of the fulllength proteins, macromolecular signaling complexes, and the lipidome is only beginning to be unraveled and represents a target of therapeutic development. This review brings together recent findings and classical concepts to concisely summarize the lipid-binding domain field while illustrating where the field is headed and how the gaps may be filled in with new technologies.-Stahelin, R. V. Lipid binding domains: more than simple lipid effectors. J. Lipid Res. 2009. 50: S299-S304.

A C2 domain protein kinase initiates phagocytosis in the protozoan parasite Entamoeba histolytica

“…2f,g). These findings are consistent with the properties of other C2-domain-containing proteins, in which binding to phosphatidylserine is mediated through the C2 domain 34,35 . We conclude from these results that EhCaBP1 binds lipids through EhC2PK and this interaction is lipid-specific and requires the presence of Ca 2 + .…”

Phosphatidylserine Stimulates Ceramide 1-Phosphate (C1P) Intermembrane Transfer by C1P Transfer Proteins

“…This arrangement keeps the lipid chains embedded in the membrane while the protein interacts with the phosphoglyceride headgroup. LBDs help target and tether various peripheral amphitropic proteins to select intracellular membrane sites (22)(23)(24)(25)(26)(27). Our experimental data support the idea of POPS functioning as a membrane tethering site that helps orient ACD11 and CPTP in ways that optimize function.…”

“…ACD11, CPTP, and GLTP are considered to be amphitropic proteins because their functionality involves translocation on/off membranes to bind and release the sphingolipid cargo (19 -21). Amphitropic proteins often contain so-called lipid binding domains (LBDs) that bind specific phosphoglyceride headgroups within membranes to help target and tether to select cell membrane destinations (22)(23)(24)(25)(26)(27). LBDs, such as the C1, C2, PH, PX, and FYVE domains, differ structurally from the GLTP-fold.…”

Site-directed Mutagenesis Shows the Significance of Interactions with Phospholipids and the G-protein OsYchF1 for the Physiological Functions of the Rice GTPase-activating Protein 1 (OsGAP1)

“…To facilitate the targeting of regulatory proteins to specific membranes and cellular compartments, various lipidbinding domains have evolved (1)(2)(3)(4). There are at least 11 lipidbinding domains, among which the eukaryote-specific C2 domain is the second most abundant (3).…”

“…To facilitate the targeting of regulatory proteins to specific membranes and cellular compartments, various lipidbinding domains have evolved (1)(2)(3)(4). There are at least 11 lipidbinding domains, among which the eukaryote-specific C2 domain is the second most abundant (3). It is characterized by a ␤-sandwich structure connected by surface loops comprising eight primary ␤-strands and one ␣-helix that may exist in a conserved position among the same family of C2 domain (4,5).…”