Sphingolipid transfer proteins defined by the GLTP-fold

Lucy Malinina, Dhirendra K. Simanshu, Xiuhong Zhai, Valeria R. Samygina, Ravikanth Kamlekar, Roopa Kenoth, Borja Ochoa-Lizarralde, Margarita L. Malakhova, Julian G. Molotkovsky, Dinshaw J. Patel, Rhoderick E. Brown

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Glycolipid transfer proteins (GLTPs) originally were identified as small (∼24 kDa), soluble, amphitropic proteins that specifically accelerate the intermembrane transfer of glycolipids. GLTPs and related homologs now are known to adopt a unique, helically dominated, two-layer 'sandwich' architecture defined as the GLTP-fold that provides the structural underpinning for the eukaryotic GLTP superfamily. Recent advances now provide exquisite insights into structural features responsible for lipid headgroup selectivity as well as the adaptability of the hydrophobic compartment for accommodating hydrocarbon chains of differing length and unsaturation. A new understanding of the structural versatility and evolutionary premium placed on the GLTP motif has emerged. Human GLTP-motifs have evolved to function not only as glucosylceramide binding/transferring domains for phosphoinositol 4-phosphate adaptor protein-2 during glycosphingolipid biosynthesis but also as selective binding/transfer proteins for ceramide-1-phosphate. The latter, known as ceramide-1-phosphate transfer protein, recently has been shown to form GLTP-fold while critically regulating Group-IV cytoplasmic phospholipase A2 activity and pro-inflammatory eicosanoid production.

Original languageEnglish (US)
Pages (from-to)281-322
Number of pages42
JournalQuarterly Reviews of Biophysics
Volume48
Issue number3
DOIs
StatePublished - Mar 23 2015

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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