title: The minimal domain of adipose triglyceride lipase (ATGL) ranges until leucine 254 and can be activated and inhibited by CGI-58 and G0S2, respectively.
abstract: Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme of lipolysis. ATGL specifically hydrolyzes triacylglycerols (TGs), thereby generating diacylglycerols and free fatty acids. ATGL's enzymatic activity is co-activated by the protein comparative gene identification-58 (CGI-58) and inhibited by the protein G0/G1 switch gene 2 (G0S2). The enzyme is predicted to act through a catalytic dyad (Ser47, Asp166) located within the conserved patatin domain (Ile10-Leu178). Yet, neither an experimentally determined 3D structure nor a model of ATGL is currently available, which would help to understand how CGI-58 and G0S2 modulate ATGL's activity. In this study we determined the minimal active domain of ATGL. This minimal fragment of ATGL could still be activated and inhibited by CGI-58 and G0S2, respectively. Furthermore, we show that this minimal domain is sufficient for protein-protein interaction of ATGL with its regulatory proteins. Based on these data, we generated a 3D homology model for the minimal domain. It strengthens our experimental finding that amino acids between Leu178 and Leu254 are essential for the formation of a stable protein domain related to the patatin fold. Our data provide insights into the structure-function relationship of ATGL and indicate higher structural similarities in the N-terminal halves of mammalian patatin-like phospholipase domain containing proteins, (PNPLA1, -2,- 3 and -5) than originally anticipated.
authors: Institute of Molecular Biosciences, University of Graz, Graz, Austria.
authors: Irina
authors: I
authors: Cornaciu
authors: Andras
authors: A
authors: Boeszoermenyi
authors: Hanna
authors: H
authors: Lindermuth
authors: Harald M
authors: HM
authors: Nagy
authors: Ines K
authors: IK
authors: Cerk
authors: Catharina
authors: C
authors: Ebner
authors: Barbara
authors: B
authors: Salzburger
authors: Astrid
authors: A
authors: Gruber
authors: Martina
authors: M
authors: Schweiger
authors: Rudolf
authors: R
authors: Zechner
authors: Achim
authors: A
authors: Lass
authors: Robert
authors: R
authors: Zimmermann
authors: Monika
authors: M
authors: Oberer
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology*; D003001:Cloning, Molecular; D004789:Enzyme Activation; D006868:Hydrolysis; D007930:Leucine / Q000378:metabolism*; D008049:Lipase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008066:Lipolysis; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014280:Triglycerides / Q000378:metabolism; D000217:Acyltransferases
chemical_list: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D018797:Cell Cycle Proteins; D007930:Leucine; D008049:Lipase; D011994:Recombinant Proteins; D014280:Triglycerides; C508072:G0S2 protein, mouse; C492986:Abhd5 protein, mouse; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases