PMID: 9159117May 27, 1997Paper

A molecular biology-based approach to resolve the subunit orientation of lipoprotein lipase

Proceedings of the National Academy of Sciences of the United States of America
H WongMichael C Schotz

Abstract

The subunit orientation of a dimeric enzyme influences the mechanism of action and function. To determine the subunit arrangement of lipoprotein lipase (LPL), a molecular biology-based approach was initiated. An eight amino acid linker region was engineered between two LPL monomers and expressed in COS-7 cells. The resultant tandem-repeat molecule (LPLTR) was lipolytically active and had kinetic parameters, salt inhibition, cofactor-dependent activity, heparin-binding characteristics, and a functional unit size very similar to the expressed native human enzyme. By these criteria, LPLTR was the functional equivalent of native LPL. Considering the length of the linker peptide (no more than 24 A), monomers in the tethered molecule were restricted to a head-to-tail subunit arrangement. Since LPLTR demonstrated native enzyme-like properties while constrained to this subunit arrangement, these results provide the first compelling evidence that native LPL monomers are arranged in a head-to-tail subunit orientation within the active dimer. Thus, LPL function in physiology, lipolysis, and binding to cell-surface components must now be addressed with this subunit orientation in mind. The utility of the tandem-repeat approach to resolve t...Continue Reading

References

Jan 1, 1975·Methods in Enzymology·C Olive, H R Levy
May 1, 1978·The Biochemical Journal·P AshbyD S Robinson
Oct 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·U BeisiegelG Bengtsson-Olivecrona
Mar 1, 1991·The Journal of Clinical Endocrinology and Metabolism·R A HegeleP W Connelly
Dec 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·H WongM C Schotz
Mar 27, 1987·Science·K L WionR M Lawn
Apr 1, 1994·Current Opinion in Lipidology·S Santamarina-Fojo, K A Dugi
Jun 7, 1994·Proceedings of the National Academy of Sciences of the United States of America·M Sahin-TóthH R Kaback
Apr 2, 1996·Proceedings of the National Academy of Sciences of the United States of America·J E Lindsley

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Citations

Apr 12, 2005·Cell Calcium·Nicholas C SpitzerCory M Root
Oct 1, 2013·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Erika SawanoTomoko Tashiro
Dec 29, 2012·Neuropharmacology·Laura N BorodinskyEduardo Bouth Sequerra
Feb 6, 2004·Progress in Neurobiology·Rafael Gutiérrez
Sep 13, 2001·Journal of Molecular Graphics & Modelling·H RazzaghiM I Kamboh
Jan 16, 2009·International Journal of Obesity : Journal of the International Association for the Study of Obesity·M Lafontan
Mar 30, 2001·European Journal of Biochemistry·T Osterlund
Jul 2, 2009·The Journal of Biological Chemistry·Nathalie GriffonDaniel J Rader
Apr 29, 2000·Current Opinion in Lipidology·D J Rader, M Jaye
Mar 13, 2010·Current Opinion in Lipidology·Mark H DoolittleMiklós Péterfy
Mar 12, 2013·Genes & Development·Stephen G Young, Rudolf Zechner
Mar 31, 2011·Journal of Lipid Research·Osnat Ben-ZeevMiklós Péterfy
May 13, 2011·Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics·Roger S HolmesLaura A Cox
Mar 21, 2016·Biochimica Et Biophysica Acta·Amy Pei-Ling ChiuBrian Rodrigues
Dec 3, 2014·Atherosclerosis·Yuan LiChao-Ke Tang
Dec 3, 2014·Biochimica Et Biophysica Acta·Ying Wang, Brian Rodrigues
Jun 10, 2014·Biochemical and Biophysical Research Communications·Melissa A Babilonia-Rosa, Saskia B Neher
Jul 2, 2002·Journal of Lipid Research·Howard Wong, Michael C Schotz
May 10, 2006·Journal of Lipid Research·Nathalie GriffonDaniel J Rader
Feb 9, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Markku O PentikäinenPetri T Kovanen
Sep 24, 2005·The Journal of Biological Chemistry·Liyan ZhangGunilla Olivecrona
Mar 7, 2006·The Journal of Biological Chemistry·Shallee PageAndré Bensadoun
Mar 26, 2009·American Journal of Physiology. Endocrinology and Metabolism·Hong Wang, Robert H Eckel
Mar 10, 2019·Proceedings of the National Academy of Sciences of the United States of America·Anne P BeigneuxStephen G Young
Feb 9, 2020·Proceedings of the National Academy of Sciences of the United States of America·Kristian K KristensenMichael Ploug
Aug 21, 2013·The Journal of Biological Chemistry·Michael J LaffertySaskia B Neher
Dec 6, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Daniel Prieto, Pablo Oppezzo
Dec 19, 2018·Proceedings of the National Academy of Sciences of the United States of America·Gabriel BirraneMuthuraman Meiyappan
Jul 4, 2019·Cell Metabolism·Stephen G YoungMichael Ploug
Dec 6, 2020·Trends in Endocrinology and Metabolism : TEM·Shuangcheng Alivia WuLing Qi
Jan 6, 2018·Biochemistry·Cassandra K HayneSaskia B Neher

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