The liganding of glycolipid transfer protein is controlled by glycolipid acyl structure

Lucy Malinina, Margarita L. Malakhova, Alex T. Kanack, Min Lu, Ruben Abagyan, Rhoderick E. Brown, Dinshaw J. Patel

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1996-2011
Number of pages16
JournalPLoS biology
Issue number11
StatePublished - Nov 2006

Fingerprint Dive into the research topics of 'The liganding of glycolipid transfer protein is controlled by glycolipid acyl structure'. Together they form a unique fingerprint.

Cite this