HGNC Approved Gene Symbol: GLTP
Cytogenetic location: 12q24.11 Genomic coordinates (GRCh38): 12:109,850,945-109,880,541 (from NCBI)
Glycolipid transfer protein is a soluble 24-kD protein that selectively accelerates the intermembrane transfer of glycolipids in vitro (Li et al., 2004).
Lin et al. (2000) cloned full-length bovine and porcine Gltp cDNAs encoding identical 209-amino acid proteins. Hydropathy plot analysis indicated that Gltp has 4 hydrophobic segments that may interact with membranes. Northern blot analysis detected Gltp expression in all bovine tissues examined, with highest expression in cerebrum. Expression was low in liver and heart muscles, respectively. Li et al. (2004) cloned human GLTP.
Li et al. (2004) used fluorescence spectroscopy to elucidate global conformational changes in GLTP that accompany GLTP folding into an active conformational state and more subtle conformational changes that play a role in GLTP-mediated transfer of glycolipids between membranes.
Crystal Structure
Malinina et al. (2004) reported the crystal structure of apo-GLTP (1.65-angstrom resolution) and lactosylceramide-bound GLTP (1.95-angstrom), in which the bound glycosphingolipid is sandwiched, after adaptive recognition, within a previously unknown 2-layer all-alpha-helical topology. Glycosphingolipid binding specificity is achieved through recognition and anchoring of the sugar-amide headgroup to the GLTP recognition center by hydrogen bond networks and hydrophobic contacts, and encapsulation of both lipid chains, in a precisely oriented manner within a 'molded-to-fit' hydrophobic tunnel. Mutation and functional analyses of residues in the glycolipid recognition center and within the hydrophobic tunnel supported a framework for understanding how GLTPs acquire and release glycosphingolipids during lipid intermembrane transfer and presentation processes.
Glycolipid transfer proteins, such as GLTP, catalyze the transfer of glycosphingolipids and glycoglycerolipids between donor and acceptor membranes. Using fluorescence resonance energy transfer, Mattjus et al. (2000) assayed purified bovine brain Gltp activity in the transfer of fluorescence-labeled galactosylsphingosine between donor and acceptor vesicles. Transfer was significantly inhibited by negatively charged lipids. Kinetic data indicated that the off-rate of Gltp from vesicles containing the glycosphingolipid controls the overall rate of the transfer event.
Simanshu et al. (2013) stated that the GLTP gene has 5 exons.
Simanshu et al. (2013) stated that the GLTP gene maps to chromosome 12q24.11.
Li, X. M., Malakhova, M. L., Lin, X., Pike, H. M., Chung, T., Molotkovsky, J. G., Brown, R. E. Human glycolipid transfer protein: probing conformation using fluorescence spectroscopy. Biochemistry 43: 10285-10294, 2004. [PubMed: 15287756] [Full Text: https://doi.org/10.1021/bi0495432]
Lin, X., Mattjus, P., Pike, H. M., Windebank, A. J., Brown, R. E. Cloning and expression of glycolipid transfer protein from bovine and porcine brain. J. Biol. Chem. 275: 5104-5110, 2000. [PubMed: 10671554] [Full Text: https://doi.org/10.1074/jbc.275.7.5104]
Malinina, L., Malakhova, M. L., Teplov, A., Brown, R. E., Patel, D. J. Structural basis for glycosphingolipid transfer specificity. Nature 430: 1048-1053, 2004. [PubMed: 15329726] [Full Text: https://doi.org/10.1038/nature02856]
Mattjus, P., Pike, H. M., Molotkovsky, J. G., Brown, R. E. Charged membrane surfaces impede the protein-mediated transfer of glycosphingolipids between phospholipid bilayers. Biochemistry 39: 1067-1075, 2000. [PubMed: 10653652] [Full Text: https://doi.org/10.1021/bi991810u]
Simanshu, D. K., Kamlekar, R. K., Wijesinghe, D. S., Zou, X., Zhai, X., Mishra, S. K., Molotkovsky, J. G., Malinina, L., Hinchcliffe, E. H., Chalfant, C. E., Brown, R. E., Patel, D. J. Non-vesicular trafficking by a ceramide-1-phosphate transfer protein regulates eicosanoids. (Letter) Nature 500: 463-467, 2013. [PubMed: 23863933] [Full Text: https://doi.org/10.1038/nature12332]