The liganding of glycolipid transfer protein is controlled by glycolipid acyl structure Journal Article
| Authors: | Malinina, L.; Malakhova, M. L.; Kanack, A. T.; Lu, M.; Abagyan, R.; Brown, R. E.; Patel, D. J. |
| Article Title: | The liganding of glycolipid transfer protein is controlled by glycolipid acyl structure |
| Abstract: | 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. |
| Keywords: | carrier protein; molecular genetics; metabolism; structure activity relation; structure-activity relationship; chemistry; molecular sequence data; nucleotide sequence; carrier proteins; ligand; ligands; base sequence; binding site; crystallography, x-ray; binding sites; protein secondary structure; sphingosine; x ray crystallography; protein structure, secondary; models, chemical; glycolipid; lipid transfer protein; glycolipids; chemical model |
| Journal Title: | PLoS Biology |
| Volume: | 4 |
| Issue: | 11 |
| ISSN: | 1544-9173 |
| Publisher: | Public Library of Science |
| Date Published: | 2006-11-01 |
| Start Page: | 1996 |
| End Page: | 2011 |
| Language: | English |
| DOI: | 10.1371/journal.pbio.0040362 |
| PUBMED: | 17105344 |
| PROVIDER: | scopus |
| PMCID: | PMC1618416 |
| DOI/URL: | |
| Notes: | --- - e362 - "Cited By (since 1996): 15" - "Export Date: 4 June 2012" - "Source: Scopus" |
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