Download MendeleyThe liganding of glycolipid transfer protein is controlled by glycolipid acyl structure.
Malinina, L., Malakhova, M.L., Kanack, A.T., Lu, M., Abagyan, R., Brown, R.E., Patel, D.J.(2006) PLoS Biol 4: e362-e362
- PubMed: 17105344
- DOI: https://doi.org/10.1371/journal.pbio.0040362
- Primary Citation of Related Structures:
2EUK, 2EUM, 2EVD, 2EVL, 2EVS, 2EVT - PubMed 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.
Organizational Affiliation:
Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America.
