A molecular caliper mechanism for determining very long-chain Denic V, Weissman JS Cell, 2007-08-27, PMID 17719544 PubMed  | Full text | Export to EndNote | PDF

Combined rating: 93% (1 Vote)

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.

Title: Author: Document type: Journal ClubResearch talk Summary: (Not mandatory) Upload document:   (Accepted file formats are Pdf, Powerpoint and Word.)

 Evaluate this paper
 Your evalution is anonymous and cannot be linked to your profile or webpage.