5A4H

Solution structure of the lipid droplet anchoring peptide of CGI-58 bound to DPC micelles

Summary for 5A4H

• Entry DOI: 10.2210/pdb5a4h/pdb
• NMR Information: BMRB: 25684
• Descriptor: 1-ACYLGLYCEROL-3-PHOSPHATE O-ACYLTRANSFERASE ABHD5 (1 entity in total)
• Functional Keywords: transferase, cgi-58, abhd5, lipid droplet anchor, solution structure
• Biological source: MUS MUSCULUS (HOUSE MOUSE)
• Cellular location: Cytoplasm: Q9DBL9
• Total number of polymer chains: 1
• Total formula weight: 3981.32

Authors

Boeszoermenyi, A.,Arthanari, H.,Wagner, G.,Nagy, H.M.,Zangger, K.,Lindermuth, H.,Oberer, M. (deposition date: 2015-06-09, release date: 2015-09-16, Last modification date: 2024-05-15)

Primary citation

Boeszoermenyi, A.,Nagy, H.M.,Arthanari, H.,Pillip, C.J.,Lindermuth, H.,Luna, R.E.,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., 290:26361-, 2015

PubMed 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 β-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.

PubMed: 26350461
DOI: 10.1074/JBC.M115.682203

Experimental method

SOLUTION NMR