Structure and function of lysosomal phospholipase A2 and lecithin:cholesterol acyltransferase

Nature Communications
Alisa GlukhovaJohn J G Tesmer

Abstract

Lysosomal phospholipase A2 (LPLA2) and lecithin:cholesterol acyltransferase (LCAT) belong to a structurally uncharacterized family of key lipid-metabolizing enzymes responsible for lung surfactant catabolism and for reverse cholesterol transport, respectively. Whereas LPLA2 is predicted to underlie the development of drug-induced phospholipidosis, somatic mutations in LCAT cause fish eye disease and familial LCAT deficiency. Here we describe several high-resolution crystal structures of human LPLA2 and a low-resolution structure of LCAT that confirms its close structural relationship to LPLA2. Insertions in the α/β hydrolase core of LPLA2 form domains that are responsible for membrane interaction and binding the acyl chains and head groups of phospholipid substrates. The LCAT structure suggests the molecular basis underlying human disease for most of the known LCAT missense mutations, and paves the way for rational development of new therapeutics to treat LCAT deficiency, atherosclerosis and acute coronary syndrome.

References

Apr 1, 1992·Protein Engineering·D L OllisJ Schrag
Mar 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·O L Francone, C J Fielding
Jul 5, 1990·Journal of Molecular Biology·D E StewartJ E Wampler
Feb 15, 1997·Structure·J D SchragA McPherson
Sep 24, 1999·The Biochemical Journal·J L Arpigny, K E Jaeger
Dec 23, 1999·Current Opinion in Structural Biology·M Nardini, B W Dijkstra
May 23, 2001·Archives of Biochemistry and Biophysics·K R MurrayA G Lacko
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·N A BakerJ A McCammon
Sep 28, 2002·Acta Crystallographica. Section D, Biological Crystallography·Thomas R Schneider, George M Sheldrick
Jun 25, 2004·Nucleic Acids Research·Todd J DolinskyNathan A Baker
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Aug 6, 2004·The Journal of Biological Chemistry·Akira AbeJames A Shayman
Jul 14, 2006·Journal of Lipid Research·Akira AbeJames A Shayman
Aug 2, 2006·Molecular and Cellular Biology·Miki HiraokaJames A Shayman
Jul 14, 2007·Journal of Lipid Research·Akira AbeJames A Shayman
Mar 27, 2009·Journal of Lipid Research·Akira Abe, James A Shayman
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Apr 23, 2010·Journal of Lipid Research·Akira AbeJames A Shayman
Jul 8, 2010·The Journal of Pharmacology and Experimental Therapeutics·Xavier RoussetAlan T Remaley
Nov 16, 2010·Progress in Lipid Research·James A ShaymanAkira Abe
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Martyn D WinnKeith S Wilson
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Garib N MurshudovAlexei A Vagin
Dec 23, 2011·Atherosclerosis·Laura CalabresiGuido Franceschini
May 9, 2012·Journal of Lipid Research·Sandra Kunnen, Miranda Van Eck
Sep 11, 2012·Biochimica Et Biophysica Acta·James A Shayman, Akira Abe
Mar 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Crina PaduraruPeter Cresswell
May 24, 2014·Nature Reviews. Drug Discovery·Bronwyn A KingwellNorman E Miller
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor

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Citations

Dec 27, 2016·Nature Structural & Molecular Biology·Stefan BibowRoland Riek
Feb 27, 2016·PloS One·Alice OssoliAlan T Remaley
Dec 21, 2016·Journal of Lipid Research·Akira AbeJames A Shayman
Jul 22, 2015·Journal of Lipid Research·Derek E PiperNigel P C Walker
Feb 14, 2018·Journal of Lipid Research·Marco G CasteleijnArtturi Koivuniemi
Sep 9, 2017·Annals of Clinical Biochemistry·Toshihiro SakuraiAlan T Remaley
May 5, 2018·Journal of Lipid Research·Vania Hinkovska-GalchevaJames A Shayman
Jun 4, 2017·The Journal of Pharmacology and Experimental Therapeutics·Lita A FreemanAlan T Remaley
Dec 24, 2015·The Journal of Biological Chemistry·Viviana PszennyIsabelle Coppens
Jun 4, 2018·Nucleic Acids Research·Wei TianJie Liang
Feb 20, 2020·Current Opinion in Lipidology·Lita A FreemanAlan T Remaley
Aug 14, 2019·Biological Chemistry·Bernadette Breiden, Konrad Sandhoff
Feb 6, 2016·Current Opinion in Lipidology·Daniel Gaudet
May 31, 2020·Journal of Bioenergetics and Biomembranes·Liangtong LiFulin Liu
Jun 17, 2020·The Plant Journal : for Cell and Molecular Biology·Lucas J FalarzGuanqun Chen
Aug 24, 2018·The Journal of Nutrition·Emily K HeyingSherry A Tanumihardjo
Mar 27, 2019·AIChE Journal·Madolyn L MacDonaldKelvin H Lee
Aug 28, 2020·Metabolomics : Official Journal of the Metabolomic Society·Inger Ødum NielsenKenji Maeda
Aug 28, 2020·International Journal of Molecular Sciences·Lars KaiserHans-Peter Deigner
Nov 27, 2015·Journal of Atherosclerosis and Thrombosis·Alice OssoliLaura Calabresi
Dec 4, 2020·Journal of Lipid Research·Tommaso LaurenziIvano Eberini
Feb 2, 2021·Journal of Lipid Research·Tommaso LaurenziIvano Eberini
Aug 11, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Akira AbeYouichi Niimura
May 25, 2021·Frontiers in Immunology·Ana Carolina MotaBernhard Brüne
Jun 5, 2021·Journal of Lipid Research·Vania Hinkovska-GalchevaJames A Shayman
Mar 5, 2019·Biochemistry·Renee A BouleyJohn J G Tesmer

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Methods Mentioned

BETA
deacylation
glycosylation
transfection

Software Mentioned

AutoSol
CCP4
MolProbity
Aimless
UCSF Chimera
ImageJ
Coot
PHASER
GraphPad Prism
PyMOL Molecular Graphics System

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