How α-helical motifs form functionally diverse lipid-binding compartments

Lucy Malinina, Dinshaw J. Patel, Rhoderick E. Brown

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Lipids are produced site-specifically in cells and then distributed nonrandomly among membranes via vesicular and nonvesicular trafficking mechanisms. The latter involves soluble amphitropic proteins extracting specific lipids from source membranes to function as molecular solubilizers that envelope their insoluble cargo before transporting it to destination sites. Lipid-binding and lipid transfer structural motifs range from multi-β-strand barrels, to β-sheet cups and baskets covered by α-helical lids, to multi-α-helical bundles and layers. Here, we focus on how α-helical proteins use amphipathic helical layering and bundling to form modular lipid-binding compartments and discuss the functional consequences. Preformed compartments generally rely on intramolecular disulfide bridging to maintain conformation (e.g., albumins, nonspecific lipid transfer proteins, saposins, nematode polyprotein allergensantigens). Insights into nonpreformed hydrophobic compartments that expand and adapt to accommodate a lipid occupant are few and provided mostly by the three-layer, α-helical ligand-binding domain of nuclear receptors. The simple but elegant and nearly ubiquitous two-layer, α-helical glycolipid transfer protein (GLTP)-fold now further advances understanding.

Original languageEnglish (US)
Pages (from-to)609-636
Number of pages28
JournalAnnual Review of Biochemistry
Volume86
DOIs
StatePublished - Jun 20 2017

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Keywords

  • Albumins
  • Fixed versus expandable hydrophobic pockets
  • GLTP-fold
  • Lipid headgroup recognition centers
  • Nematode polyprotein allergensantigens
  • Nonspecific lipid transfer proteins
  • Nuclear receptor ligand-binding domains
  • Protein helical layeringbundling
  • Saposins
  • Sphingolipid transfer proteins

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