Environmental Molecular Sciences Laboratory

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Structure and Assembly of Membrane Fatty Acid Elongases

Friday, October 16, 2020
Principal Investigator: 
Alex Vecchio
Lead Institution: 
University of Nebraska - Lincoln
Project ID: 

Elongation of very long chain fatty acids (VLCFAs) in mammals is directed by membrane proteins called ELOngation of Very Long chain fatty acids (ELOVLs). ELOVLs catalyze the first and rate-limiting step in VLCFA elongation, and these VLCFAs confer diverse functions to cells and help define the structures of lipids. In humans, seven ELOVL subtypes display altered substrate specificity, tissue distribution, and regulation patterns, making them critical modulators of lipid composition and fatty acid function in cells. ELOVL activity causes accumulation of VLCFAs in the brain in X-linked adrenoleukodystrophy (ALD), an orphan disease that inflicts young boys causing permanent disability and death. ELOVL mutations and polymorphisms can lead to other neurological disorders and disorders of the ear, eye, kidney, and skin. Our goal is to determine the structural basis of ELOVL assembly to resolve ELOVL function. We have stable, pure, monodisperse ELOVL complexes, and preliminary negative stain and cryo-EM data in-hand.