Structural highlights
Function
[ABHD5_MOUSE] Lysophosphatidic acid acyltransferase which functions in phosphatidic acid biosynthesis. May regulate the cellular storage of triacylglycerol through activation of the phospholipase PNPLA2. Involved in keratinocyte differentiation.[1]
Publication Abstract from PubMed
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.
Structure of a CGI-58 Motif Provides the Molecular Basis of Lipid Droplet Anchoring.,Boeszoermenyi A, Nagy HM, Arthanari H, Pillip CJ, Lindermuth H, Luna RE, Wagner G, Zechner R, Zangger K, Oberer M J Biol Chem. 2015 Oct 30;290(44):26361-72. doi: 10.1074/jbc.M115.682203. Epub, 2015 Sep 8. PMID:26350461[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lass A, Zimmermann R, Haemmerle G, Riederer M, Schoiswohl G, Schweiger M, Kienesberger P, Strauss JG, Gorkiewicz G, Zechner R. Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome. Cell Metab. 2006 May;3(5):309-19. PMID:16679289 doi:http://dx.doi.org/10.1016/j.cmet.2006.03.005
- ↑ Boeszoermenyi A, Nagy HM, Arthanari H, Pillip CJ, Lindermuth H, Luna RE, Wagner G, Zechner R, Zangger K, Oberer M. Structure of a CGI-58 Motif Provides the Molecular Basis of Lipid Droplet Anchoring. J Biol Chem. 2015 Oct 30;290(44):26361-72. doi: 10.1074/jbc.M115.682203. Epub, 2015 Sep 8. PMID:26350461 doi:http://dx.doi.org/10.1074/jbc.M115.682203
