Boeszoermenyi_2015_J.Biol.Chem_290_26361

Reference

Title : Structure of a CGI-58 Motif Provides the Molecular Basis of Lipid Droplet Anchoring - Boeszoermenyi_2015_J.Biol.Chem_290_26361
Author(s) : Boeszoermenyi A , Nagy HM , Arthanari H , Pillip CJ , Lindermuth H , Luna RE , Wagner G , Zechner R , Zangger K , Oberer M
Ref : Journal of Biological Chemistry , 290 :26361 , 2015
Abstract :

Triacylglycerols (TGs) stored in lipid droplets (LDs) are hydrolyzed in a highly regulated metabolic process called lipolysis to free fatty acids that serve as energy substrates for beta-oxidation, precursors for membrane lipids and signaling molecules. Comparative gene identification-58 (CGI-58) stimulates the enzymatic activity of adipose triglyceride lipase (ATGL), which catalyzes the hydrolysis of TGs to diacylglycerols and free fatty acids. In adipose tissue, protein-protein interactions between CGI-58 and the LD coating protein perilipin 1 restrain the ability of CGI-58 to activate ATGL under basal conditions. Phosphorylation of perilipin 1 disrupts these interactions and mobilizes CGI-58 for the activation of ATGL. We have previously demonstrated that the removal of a peptide at the N terminus (residues 10-31) of CGI-58 abrogates CGI-58 localization to LDs and CGI-58-mediated activation of ATGL. Here, we show that this tryptophan-rich N-terminal peptide serves as an independent LD anchor, with its three tryptophans serving as focal points of the left (harboring Trp(21) and Trp(25)) and right (harboring Trp(29)) anchor arms. The solution state NMR structure of a peptide comprising the LD anchor bound to dodecylphosphocholine micelles as LD mimic reveals that the left arm forms a concise hydrophobic core comprising tryptophans Trp(21) and Trp(25) and two adjacent leucines. Trp(29) serves as the core of a functionally independent anchor arm. Consequently, simultaneous tryptophan alanine permutations in both arms abolish localization and activity of CGI-58 as opposed to tryptophan substitutions that occur in only one arm.

PubMedSearch : Boeszoermenyi_2015_J.Biol.Chem_290_26361
PubMedID: 26350461
Gene_locus related to this paper: human-ABHD5

Related information

Gene_locus human-ABHD5
Structure 5A4H

Citations formats

Boeszoermenyi A, Nagy HM, Arthanari H, Pillip CJ, Lindermuth H, Luna RE, Wagner G, Zechner R, Zangger K, Oberer M (2015)
Structure of a CGI-58 Motif Provides the Molecular Basis of Lipid Droplet Anchoring
Journal of Biological Chemistry 290 :26361

Boeszoermenyi A, Nagy HM, Arthanari H, Pillip CJ, Lindermuth H, Luna RE, Wagner G, Zechner R, Zangger K, Oberer M (2015)
Journal of Biological Chemistry 290 :26361