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 language||English (US)|
|Number of pages||28|
|Journal||Annual Review of Biochemistry|
|State||Published - Jun 20 2017|
Bibliographical noteFunding Information:
The GLTP-fold research summarized here was supported by NIH/NIGMSGM45928 (R.E.B.), NIH/NCI-CA121493 (D.J.P., R.E.B.), NIH/NHLBI-HL125353 (R.E.B., D.J.P.), Memorial Sloan Kettering Cancer Center Core grant P30CA008748 (D.J.P.), Spanish Ministerio de Ciencia e Innovacion BFU2010-17711 (L.M.), Russian Foundation for Basic Research 09-04-00313, 12-04-00168, and 15-04-07415, Abby Rockefeller Mauze Trust (D.J.P.), Maloris Foundation (D.J.P.), and Hormel Foundation (R.E.B.).
© 2017 by Annual Reviews.
- Fixed versus expandable hydrophobic pockets
- Lipid headgroup recognition centers
- Nematode polyprotein allergensantigens
- Nonspecific lipid transfer proteins
- Nuclear receptor ligand-binding domains
- Protein helical layeringbundling
- Sphingolipid transfer proteins