| 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]
Publication Abstract from PubMed
Human glycolipid transfer protein (GLTP) fold represents a novel structural motif for lipid binding/transfer and reversible membrane translocation. GLTPs transfer glycosphingolipids (GSLs) that are key regulators of cell growth, division, surface adhesion, and neurodevelopment. Herein, we report structure-guided engineering of the lipid binding features of GLTP. New crystal structures of wild-type GLTP and two mutants (D48V and A47D ||D48V), each containing bound N-nervonoyl-sulfatide, reveal the molecular basis for selective anchoring of sulfatide (3-O-sulfo-galactosylceramide) by D48V-GLTP. Directed point mutations of "portal entrance" residues, A47 and D48, reversibly regulate sphingosine access to the hydrophobic pocket via a mechanism that could involve homodimerization. "Door-opening" conformational changes by phenylalanines within the hydrophobic pocket are revealed during lipid encapsulation by new crystal structures of bona fide apo-GLTP and GLTP complexed with N-oleoyl-glucosylceramide. The development of "engineered GLTPs" with enhanced specificity for select GSLs provides a potential new therapeutic approach for targeting GSL-mediated pathologies.
Enhanced selectivity for sulfatide by engineered human glycolipid transfer protein.,Samygina VR, Popov AN, Cabo-Bilbao A, Ochoa-Lizarralde B, Goni-de-Cerio F, Zhai X, Molotkovsky JG, Patel DJ, Brown RE, Malinina L Structure. 2011 Nov 9;19(11):1644-54. PMID:22078563[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
- ↑ Samygina VR, Popov AN, Cabo-Bilbao A, Ochoa-Lizarralde B, Goni-de-Cerio F, Zhai X, Molotkovsky JG, Patel DJ, Brown RE, Malinina L. Enhanced selectivity for sulfatide by engineered human glycolipid transfer protein. Structure. 2011 Nov 9;19(11):1644-54. PMID:22078563 doi:10.1016/j.str.2011.09.011
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