How α-helical motifs form functionally diverse lipid-binding compartments Journal Article
| Authors: | Malinina, L.; Patel, D. J.; Brown, R. E. |
| Article 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 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. © 2017 by Annual Reviews. |
| Keywords: | carrier protein; genetics; nonhuman; binding affinity; protein domain; animal; metabolism; animals; gene expression; lipid; protein binding; chemistry; albumins; amino acid sequence; antigen; antigens; carrier proteins; binding site; models, molecular; lipids; binding sites; conformational transition; conformation; allergens; cell nucleus receptor; lipid metabolism; ligand binding; biological transport; molecular model; lipid bilayer; albuminoid; protein domains; glycolipid; lipid transfer protein; lipid transport; serum albumin; transport at the cellular level; alpha helix; sphingolipid; beta sheet; polyprotein; allergen; ceramide 1 phosphate; humans; human; priority journal; article; 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; phorbol dibutyrate; sphingolipid activator protein; sterol carrier protein 2; sterol carrier proteins; protein conformation, alpha-helical; protein conformation, beta-strand |
| Journal Title: | Annual Review of Biochemistry |
| Volume: | 86 |
| ISSN: | 0066-4154 |
| Publisher: | Annual Reviews |
| Date Published: | 2017-06-01 |
| Start Page: | 609 |
| End Page: | 636 |
| Language: | English |
| DOI: | 10.1146/annurev-biochem-061516-044445 |
| PUBMED: | 28375742 |
| PROVIDER: | scopus |
| PMCID: | PMC7935428 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 August 2017 -- Source: Scopus |
