title: How α-Helical Motifs Form Functionally Diverse Lipid-Binding Compartments.
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 allergens/antigens). 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.
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota 55912; email: lucy@hi.umn.edu , reb@umn.edu.
authors.forename: Lucy
authors.initials: L
authors.lastname: Malinina
authors.affiliation: Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065; email: pateld@mskcc.org.
authors.forename: Dinshaw J
authors.initials: DJ
authors.lastname: Patel
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, Minnesota 55912; email: lucy@hi.umn.edu , reb@umn.edu.
authors.forename: Rhoderick E
authors.initials: RE
authors.lastname: Brown
mesh_terms: D000418:Albumins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000485:Allergens / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D008958:Models, Molecular; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D000072417:Protein Domains
chemical_list: D000418:Albumins; D000485:Allergens; D000941:Antigens; D002352:Carrier Proteins; D008055:Lipids; C030363:lipid transfer protein; C072087:sterol carrier proteins
keywords: GLTP-fold; albumins; fixed versus expandable hydrophobic pockets; lipid headgroup recognition centers; nematode polyprotein allergens/antigens; nonspecific lipid transfer proteins; nuclear receptor ligand-binding domains; protein helical layering/bundling; saposins; sphingolipid transfer proteins