Glycolipid transfer proteins

Abstract

Glycolipid transfer proteins (GLTPs) are small (24 kD), soluble, ubiquitous proteins characterized by their ability to accelerate the intermembrane transfer of glycolipids in vitro. GLTP specificity encompasses both sphingoid-and glycerol-based glycolipids, but with a strict requirement that the initial sugar residue be beta-linked to the hydrophobic lipid backbone. The 3D protein structures of GLTP reveal liganded structures with unique lipid binding modes. The biochemical properties of GLTP action at the membrane surface have been studied rather comprehensively, but the biological role of GLTP remains enigmatic. What is clear is that GLTP differs distinctly from other known glycolipid-binding proteins, such as nonspecific lipid transfer proteins, lysosomal sphingolipid activator proteins, lectins, lung surfactant proteins as well as other lipid binding/transfer proteins. Based on the unique conformational architecture that targets GLTP to membranes and enables glycolipid binding, GLTP is now considered the prototypical and founding member of a new protein superfamily in eukaryotes.

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

“…The GLTPfold is a structural motif that uses an all ␣-helical, two-layer "sandwich" topology to form a single, distinct sphingolipid binding site (8,(11)(12)(13)(14). Our data indicate that PS stimulates the sphingolipid transfer activity of C1P-specific GLTP-folds (i.e.…”

Structural Determination and Tryptophan Fluorescence of Heterokaryon Incompatibility C2 Protein (HET-C2), a Fungal Glycolipid Transfer Protein (GLTP), Provide Novel Insights into Glycolipid Specificity and Membrane Interaction by the GLTP Fold

“…The involvement of Trp in GLTP functionality is well established (8,9,45,46,(51)(52)(53)(54)(55) (Fig. 2A).…”

“…HET-C2 was shown to stimulate in vitro inter-membrane transfer of galactosylceramide, but not sphingomyelin, ceramide, phosphatidylcholine, or cholesterol (7). Similar glycolipid specificity is displayed by mammalian GLTPs (8), which accomplish transfer using a distinct two-layer "sandwich motif," dominated by ␣-helices and without intramolecular disulfide bonds (9 -11). A binding site for a single glycolipid molecule consists of a sugar headgroup recognition site located where the sugaramide portion of the glycolipid is tethered via multiple hydrogen bonds to the protein's surface.…”

“…Despite conservation of so many key residues in HET-C2, subtle structural differences raised the possibility of altered selectivity for glycolipids compared with GLTP, which can transfer a variety of glycolipids of differing structural complexity (8). The only glycolipid tested earlier with HET-C2 was GalCer (7).…”

Glycolipid transfer protein: Clear structure and activity, but enigmatic function

“…Glycolipid transfer proteins (GLTPs, EC number not assigned) are water-soluble proteins of average size of 24 kDa that have been studied extensively in vitro Abe et al, 1982;Brown et al, 1990;Gammon et al, 1987;Metz and Radin, 1982). Very recently, their structural and in vitro functional properties were Abbreviations: CD, circular dichroism; DTT, dithiothreitol; Egg PC, L-a-phosphatidylcholine; FMN, flavin mononucleotide; GlcCer, glucosylceramide; GlcCerpyr, pyrene-labeled glucosylceramide; GLTP, glycolipid transfer protein; HSQC, heteronuclear single quantum correlation; Photo-CIDNP, photochemically induced dynamic nuclear polarization; PMSF, phenyl methyl sulfonylfluoride.reviewed in detail (Brown and Mattjus, 2007). These proteins have been isolated from different sources ranging from spinach chloroplasts to mammalian brain, liver and kidney (Brown et al, 1990;Sasaki, 1985Sasaki, , 1990.…”