A Molecular Caliper Mechanism for Determining Very Long-Chain Fatty Acid Length

Citations of this article
Mendeley users who have this article in their library.


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. © 2007 Elsevier Inc. All rights reserved.

Author supplied keywords




Denic, V., & Weissman, J. S. (2007). A Molecular Caliper Mechanism for Determining Very Long-Chain Fatty Acid Length. Cell, 130(4), 663–677. https://doi.org/10.1016/j.cell.2007.06.031

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free