Structure of a CGI-58 motif provides the molecular basis of lipid droplet anchoring.

The Journal of Biological Chemistry
Andras BoeszoermenyiMonika Oberer

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...Continue Reading

References

Sep 25, 1992·Proceedings of the National Academy of Sciences of the United States of America·J J EganC Londos
Jul 1, 1995·Nature Structural Biology·M B SwindellsJ M Thornton
Jan 1, 1994·Methods in Enzymology·D S Wishart, B D Sykes
Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Dec 1, 1996·Journal of Biomolecular NMR·R A LaskowskiJ M Thornton
Nov 21, 1997·Journal of Molecular Biology·P GüntertK Wüthrich
Nov 15, 2000·Quarterly Reviews of Biophysics·A E Ferentz, G Wagner
Nov 14, 2001·The Journal of Biological Chemistry·Bo-Yeon KwakHee-Won Park
Jun 18, 2003·The Journal of Cell Biology·Carole SztalrydConstantine Londos
Jul 10, 2004·Structure·Sabrina J HickenbottomJames H Hurley
Aug 5, 2004·The Journal of Biological Chemistry·Vidya SubramanianDawn L Brasaemle
Nov 20, 2004·Science·Robert ZimmermannRudolf Zechner
Dec 23, 2006·Proteins·Aneerban BhattacharyaGaetano T Montelione
Dec 26, 2006·The Journal of Biological Chemistry·James G GrannemanZhengxian Zhu
Apr 3, 2007·Journal of the American Chemical Society·Michal RespondekKlaus Zangger
Nov 7, 2007·Nucleic Acids Research·Eldon L UlrichJohn L Markley
May 1, 2008·The Journal of Biological Chemistry·Martina SchweigerRobert Zimmermann
May 9, 2008·Nucleic Acids Research·Christian ColeGeoffrey J Barton
Mar 6, 2009·Journal of Cell Science·Yi GuoTobias C Walther
Apr 30, 2009·American Journal of Physiology. Endocrinology and Metabolism·Martina SchweigerRudolf Zechner
May 23, 2009·Journal of Cell Science·Krishnakant G SoniJuan S Bonifacino
Aug 19, 2009·Chembiochem : a European Journal of Chemical Biology·Magnus FranzmannReinhard Wimmer
Dec 4, 2009·Chembiochem : a European Journal of Chemical Biology·Geoffray LabarDidier M Lambert
Dec 8, 2009·Journal of Molecular Biology·T BertrandM Mathieu
Mar 17, 2010·The Journal of Physical Chemistry. B·Christoph GöblKlaus Zangger
Nov 23, 2010·Progress in Lipid Research·Achim LassRudolf Zechner
Dec 15, 2010·The Journal of Biological Chemistry·James G GrannemanLi Zhou
Feb 11, 2011·Protein Science : a Publication of the Protein Society·Céline Schalk-HihiLawrence C Kuo
Mar 12, 2011·The Journal of Biological Chemistry·Hong WangCarole Sztalryd
Apr 16, 2011·Current Opinion in Lipidology·Monika ObererRudolf Zechner

❮ Previous
Next ❯

Citations

Mar 21, 2016·Trends in Cell Biology·Nora KoryTobias C Walther
Oct 27, 2016·International Journal of Obesity : Journal of the International Association for the Study of Obesity·B HirschmuglS Hauguel-de Mouzon
May 25, 2018·Journal of Cell Science·Francesca NardiSusan E Crawford
Feb 18, 2017·Scientific Reports·Matthew A SandersJames G Granneman
Jun 15, 2018·Breast Cancer Research : BCR·Christopher J SevinskyDouglas S Conklin
Aug 15, 2018·Proceedings of the National Academy of Sciences of the United States of America·Camille I PatakiRon R Kopito
Sep 2, 2020·Journal of Experimental & Clinical Cancer Research : CR·Manman LiangBiao Geng
Feb 27, 2020·Biology·Ben LeylandInna Khozin-Goldberg
May 1, 2019·Nature Metabolism·Stefano Romeo, David B Savage
Sep 15, 2018·Proteomics·Congyan Zhang, Pingsheng Liu
Oct 7, 2020·Annual Review of Cell and Developmental Biology·Melissa A Roberts, James A Olzmann
Nov 20, 2019·Nature Metabolism·Zegeye H JebessaJohannes Backs
Jan 10, 2018·Developmental Cell·Coline PrévostTobias C Walther
May 21, 2021·The Journal of Physical Chemistry. B·Siyoung KimJessica M J Swanson
Nov 21, 2021·Nature Metabolism·Gernot F GrabnerRudolf Zechner

❮ Previous
Next ❯

Methods Mentioned

BETA
Assay
NMR
dynamic light scattering
circular dichroism

Software Mentioned

PSVS
Jpred
hmsIST
NMRpipe
iCING
Cyana
TALOS
relax
PyMOL
CING

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.