Structural highlights
Function
[GLTP_HUMAN] Accelerates the intermembrane transfer of various glycolipids. Catalyzes the transfer of various glycosphingolipids between membranes but does not catalyze the transfer of phospholipids. May be involved in the intracellular translocation of glucosylceramides.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Glycosphingolipids (GSLs) play major roles in cellular growth and development. Mammalian glycolipid transfer proteins (GLTPs) are potential regulators of cell processes mediated by GSLs and display a unique architecture among lipid binding/transfer proteins. The GLTP fold represents a novel membrane targeting/interaction domain among peripheral proteins. Here we report crystal structures of human GLTP bound to GSLs of diverse acyl chain length, unsaturation, and sugar composition. Structural comparisons show a highly conserved anchoring of galactosyl- and lactosyl-amide headgroups by the GLTP recognition center. By contrast, acyl chain chemical structure and occupancy of the hydrophobic tunnel dictate partitioning between sphingosine-in and newly-observed sphingosine-out ligand-binding modes. The structural insights, combined with computed interaction propensity distributions, suggest a concerted sequence of events mediated by GLTP conformational changes during GSL transfer to and/or from membranes, as well as during GSL presentation and/or transfer to other proteins.
The liganding of glycolipid transfer protein is controlled by glycolipid acyl structure.,Malinina L, Malakhova ML, Kanack AT, Lu M, Abagyan R, Brown RE, Patel DJ PLoS Biol. 2006 Nov;4(11):e362. PMID:17105344[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zou X, Chung T, Lin X, Malakhova ML, Pike HM, Brown RE. Human glycolipid transfer protein (GLTP) genes: organization, transcriptional status and evolution. BMC Genomics. 2008 Feb 8;9:72. PMID:18261224 doi:1471-2164-9-72
- ↑ Rao CS, Lin X, Pike HM, Molotkovsky JG, Brown RE. Glycolipid transfer protein mediated transfer of glycosphingolipids between membranes: a model for action based on kinetic and thermodynamic analyses. Biochemistry. 2004 Nov 2;43(43):13805-15. PMID:15504043 doi:10.1021/bi0492197
- ↑ Tuuf J, Mattjus P. Human glycolipid transfer protein--intracellular localization and effects on the sphingolipid synthesis. Biochim Biophys Acta. 2007 Nov;1771(11):1353-63. Epub 2007 Sep 21. PMID:17980653 doi:S1388-1981(07)00196-5
- ↑ Malinina L, Malakhova ML, Teplov A, Brown RE, Patel DJ. Structural basis for glycosphingolipid transfer specificity. Nature. 2004 Aug 26;430(7003):1048-53. PMID:15329726 doi:10.1038/nature02856
- ↑ Malinina L, Malakhova ML, Kanack AT, Lu M, Abagyan R, Brown RE, Patel DJ. The liganding of glycolipid transfer protein is controlled by glycolipid acyl structure. PLoS Biol. 2006 Nov;4(11):e362. PMID:17105344 doi:10.1371/journal.pbio.0040362
