Rapid subunit exchange in dimeric lipoprotein lipase and properties of the inactive monomer.

The Journal of Biological Chemistry
Aivar LookeneG Olivecrona

Abstract

Lipoprotein lipase (LPL), a key enzyme in the metabolism of triglyceride-rich plasma lipoproteins, is a homodimer. Dissociation to monomers leads to loss of activity. Evidence that LPL dimers rapidly exchange subunits was demonstrated by fluorescence resonance energy transfer between lipase subunits labeled with Oregon Green and tetrametylrhodamine, respectively, and also by formation of heterodimers composed of radiolabeled and biotinylated lipase subunits captured on streptavidine-agarose. Compartmental modeling of the inactivation kinetics confirmed that rapid subunit exchange must occur. Studies of activity loss indicated the existence of a monomer that can form catalytically active dimers, but this intermediate state has not been possible to isolate and remains hypothetical. Differences in solution properties and conformation between the stable but catalytically inactive monomeric form of LPL and the active dimers were studied by static light scattering, intrinsic fluorescence, and probing with 4,4'-dianilino-1,1'-binaphtyl-5,5'-disulfonic acid and acrylamide. The catalytically inactive monomer appeared to have a more flexible and exposed structure than the dimers and to be more prone to aggregation. By limited proteolysis...Continue Reading

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Citations

Mar 13, 2010·Current Opinion in Lipidology·Mark H DoolittleMiklós Péterfy
Nov 17, 2004·BMC Physiology·Lucyna NeugerGunilla Olivecrona
Mar 31, 2011·Journal of Lipid Research·Osnat Ben-ZeevMiklós Péterfy
Jan 9, 2014·Trends in Endocrinology and Metabolism : TEM·Wieneke Dijk, Sander Kersten
Nov 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Valentina SukoninaGunilla Olivecrona
Oct 26, 2011·Biochimica Et Biophysica Acta·Min Suk KimBrian Rodrigues
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Jul 2, 2014·Biochemical and Biophysical Research Communications·Mikael LarssonGunilla Olivecrona
Sep 24, 2005·The Journal of Biological Chemistry·Liyan ZhangGunilla Olivecrona
Sep 4, 2020·Biological & Pharmaceutical Bulletin·Tomoyasu FujiiTetsuo Morita
Jun 28, 2007·American Journal of Physiology. Endocrinology and Metabolism·Gengshu WuThomas Olivecrona
Feb 9, 2020·Proceedings of the National Academy of Sciences of the United States of America·Kristian K KristensenMichael Ploug
Mar 10, 2019·Proceedings of the National Academy of Sciences of the United States of America·Anne P BeigneuxStephen G Young
Apr 26, 2020·Proceedings of the National Academy of Sciences of the United States of America·Kathryn H GunnSaskia B Neher
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Jan 6, 2018·Biochemistry·Cassandra K HayneSaskia B Neher

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