5
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      A molecular caliper mechanism for determining very long-chain fatty acid length.

      Cell

      Acetyltransferases, metabolism, Binding Sites, Coenzyme A Ligases, biosynthesis, genetics, DNA Mutational Analysis, Fatty Acids, Nonesterified, Liposomes, chemistry, Lysine, Models, Biological, Protein Binding, Protein Engineering, Protein Structure, Secondary

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Very long-chain fatty acids (VLCFAs) are essential lipids whose functional diversity is enabled by variation in their chain length. The full VLCFA biosynthetic machinery and how this machinery generates structural diversity remain elusive. Proteoliposomes reconstituted here from purified membrane components-an elongase protein (Elop), a novel dehydratase, and two reductases-catalyzed repeated rounds of two-carbon addition that elongated shorter FAs into VLCFAs whose length was dictated by the specific Elop homolog present. Mutational analysis revealed that the Elop active site faces the cytosol, whereas VLCFA length is determined by a lysine near the luminal end of an Elop transmembrane helix. By stepping the lysine residue along one face of the helix toward the cytosol, we engineered novel synthases with correspondingly shorter VLCFA outputs. Thus the distance between the active site and the lysine residue determines chain length. Our results uncover a mutationally adjustable, caliper-like mechanism that generates the repertoire of cellular VLCFAs.

          Related collections

          Author and article information

          Journal
          17719544
          10.1016/j.cell.2007.06.031

          Comments

          Comment on this article