Identification of lipid binding and lipoprotein lipase activation domains of human apoAV

2006 ◽  
Vol 143 (1-2) ◽  
pp. 22-28 ◽  
Author(s):  
Guotao Sun ◽  
Nan Bi ◽  
Guoping Li ◽  
Xuewei Zhu ◽  
Wuwei Zeng ◽  
...  
Keyword(s):  
Lipoprotein Lipase ◽  
Lipid Binding ◽  
Activation Domains

scholarly journals Structure of lipoprotein lipase in complex with GPIHBP1

2019 ◽  
Vol 116 (21) ◽  
pp. 10360-10365 ◽  
Author(s):  
Rishi Arora ◽  
Amitabh V. Nimonkar ◽  
Daniel Baird ◽  
Chunhua Wang ◽  
Chun-Hao Chiu ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Lipoprotein Lipase ◽  
Structural Information ◽  
Density Lipoprotein ◽  
Lipid Binding ◽  
Structural Basis ◽  
Maturation Factor ◽  
Lipase Maturation Factor 1 ◽  
Hydrolysis Of

Lipoprotein lipase (LPL) plays a central role in triglyceride (TG) metabolism. By catalyzing the hydrolysis of TGs present in TG-rich lipoproteins (TRLs), LPL facilitates TG utilization and regulates circulating TG and TRL concentrations. Until very recently, structural information for LPL was limited to homology models, presumably due to the propensity of LPL to unfold and aggregate. By coexpressing LPL with a soluble variant of its accessory protein glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) and with its chaperone protein lipase maturation factor 1 (LMF1), we obtained a stable and homogenous LPL/GPIHBP1 complex that was suitable for structure determination. We report here X-ray crystal structures of human LPL in complex with human GPIHBP1 at 2.5–3.0 Å resolution, including a structure with a novel inhibitor bound to LPL. Binding of the inhibitor resulted in ordering of the LPL lid and lipid-binding regions and thus enabled determination of the first crystal structure of LPL that includes these important regions of the protein. It was assumed for many years that LPL was only active as a homodimer. The structures and additional biochemical data reported here are consistent with a new report that LPL, in complex with GPIHBP1, can be active as a monomeric 1:1 complex. The crystal structures illuminate the structural basis for LPL-mediated TRL lipolysis as well as LPL stabilization and transport by GPIHBP1.

Characterization of Recombinant Wild Type and Site-Directed Mutations of Apolipoprotein C-III:  Lipid Binding, Displacement of ApoE, and Inhibition of Lipoprotein Lipase†

Biochemistry ◽  
2000 ◽  
Vol 39 (31) ◽  
pp. 9201-9212 ◽  
Author(s):  
Haiqun Liu ◽  
Philippa J. Talmud ◽  
Laurence Lins ◽  
Robert Brasseur ◽  
Gunilla Olivecrona ◽  
...  
Keyword(s):  
Lipoprotein Lipase ◽  
Lipid Binding ◽  
Wild Type ◽  
Apolipoprotein C

scholarly journals Characterization of the lipid-binding properties and lipoprotein lipase inhibition of a novel apolipoprotein C-III variant Ala23Thr

2000 ◽  
Vol 41 (11) ◽  
pp. 1760-1771 ◽  
Author(s):  
Haiqun Liu ◽  
Christine Labeur ◽  
Chun-Fang Xu ◽  
Robert Ferrell ◽  
Laurence Lins ◽  
...  
Keyword(s):  
Lipoprotein Lipase ◽  
Lipid Binding ◽  
Binding Properties ◽  
Apolipoprotein C ◽  
Lipase Inhibition

Lipid-binding proteins and lipoprotein lipase activity in human skeletal muscle: influence of physical activity and gender

2004 ◽  
Vol 97 (4) ◽  
pp. 1209-1218 ◽  
Author(s):  
Bente Kiens ◽  
Carsten Roepstorff ◽  
Jan F. C. Glatz ◽  
Arend Bonen ◽  
Peter Schjerling ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipoprotein Lipase ◽  
Binding Proteins ◽  
Mrna Level ◽  
Lipid Binding ◽  
Mrna Levels ◽  
Training Status ◽  
Fatty Acid Binding ◽  
Muscle Lipid ◽  
Lipid Binding Proteins

The protein and mRNA levels of several muscle lipid-binding proteins and the activity and mRNA level of muscle lipoprotein lipase (mLPL) were investigated in healthy, nonobese, nontrained (NT), moderately trained, and endurance-trained (ET) women and men. FAT/CD36 protein level was 49% higher ( P < 0.05) in women than in men, irrespective of training status, whereas FAT/CD36 mRNA was only higher ( P < 0.05) in women than in men in NT subjects (85%). Plasma membrane-bound fatty acid binding protein (FABPpm) content was higher in ET men compared with all other groups, whereas training status did not affect FABPpm content in women. FABPpm mRNA was higher ( P < 0.05) in NT women than in ET women and NT men. mLPL activity was not different between gender, but mLPL mRNA was 160% higher ( P < 0.001) in women than in men. mLPL activity was 48% higher ( P < 0.05) in ET than in NT subjects, irrespective of gender, in accordance with 49% higher ( P < 0.05) mLPL mRNA in ET than in NT subjects. A 90-min exercise bout induced an increase ( P < 0.05) in FAT/CD36 mRNA (∼25%) and FABPpm mRNA (∼15%) levels in all groups. The present study demonstrated that, in the NT state, women had higher muscle mRNA levels of several proteins related to muscle lipid metabolism compared with men. In the ET state, only the gender difference in mLPL mRNA persisted. FAT/CD36 protein in muscle was higher in women than in men, irrespective of training status. These findings may help explain gender differences in lipid metabolism and, furthermore, suggest that the balance between gene transcription, translation, and possibly breakdown of several proteins in muscle lipid metabolism depend on gender.

scholarly journals Unfolding of monomeric lipoprotein lipase by ANGPTL4: Insight into the regulation of plasma triglyceride metabolism

2020 ◽  
Vol 117 (8) ◽  
pp. 4337-4346 ◽  
Author(s):  
Kristian K. Kristensen ◽  
Katrine Zinck Leth-Espensen ◽  
Haydyn D. T. Mertens ◽  
Gabriel Birrane ◽  
Muthuraman Meiyappan ◽  
...  
Keyword(s):  
Lipoprotein Lipase ◽  
Lipid Binding ◽  
Carboxyl Terminus ◽  
Specific Monoclonal Antibody ◽  
Triglyceride Hydrolysis ◽  
Severe Hypertriglyceridemia ◽  
Capillary Endothelial Cells ◽  
Hydrolysis Of ◽  
Insight Into ◽  
Binding Loop

The binding of lipoprotein lipase (LPL) to GPIHBP1 focuses the intravascular hydrolysis of triglyceride-rich lipoproteins on the surface of capillary endothelial cells. This process provides essential lipid nutrients for vital tissues (e.g., heart, skeletal muscle, and adipose tissue). Deficiencies in either LPL or GPIHBP1 impair triglyceride hydrolysis, resulting in severe hypertriglyceridemia. The activity of LPL in tissues is regulated by angiopoietin-like proteins 3, 4, and 8 (ANGPTL). Dogma has held that these ANGPTLs inactivate LPL by converting LPL homodimers into monomers, rendering them highly susceptible to spontaneous unfolding and loss of enzymatic activity. Here, we show that binding of an LPL-specific monoclonal antibody (5D2) to the tryptophan-rich lipid-binding loop in the carboxyl terminus of LPL prevents homodimer formation and forces LPL into a monomeric state. Of note, 5D2-bound LPL monomers are as stable as LPL homodimers (i.e., they are not more prone to unfolding), but they remain highly susceptible to ANGPTL4-catalyzed unfolding and inactivation. Binding of GPIHBP1 to LPL alone or to 5D2-bound LPL counteracts ANGPTL4-mediated unfolding of LPL. In conclusion, ANGPTL4-mediated inactivation of LPL, accomplished by catalyzing the unfolding of LPL, does not require the conversion of LPL homodimers into monomers. Thus, our findings necessitate changes to long-standing dogma on mechanisms for LPL inactivation by ANGPTL proteins. At the same time, our findings align well with insights into LPL function from the recent crystal structure of the LPL•GPIHBP1 complex.

Heparin

1985 ◽  
Vol 05 (03) ◽  
pp. 121-126
Author(s):  
L. B. Jaques
Keyword(s):  
Lipoprotein Lipase ◽  
Antithrombin Iii

ZusammenfassungIn vivo bewirkt Heparin das Auftreten einer Lipoprotein-Lipase, einer Diaminoxydase (Histaminase) und anderer Enzyme. In Tierversuchen konnten viele günstige Wirkungen von Heparin und Heparinoiden aufgezeigt werden, wie z.B. Schutzeffekte gegen toxische Medikamente und Prozeduren, gegen Überempfindlichkeitsreaktionen, Änderungen von Hormoneffekten und die Erhöhung der negativen elektrischen Ladung von Körperzellen. Die Einzelwirkungen sind für bestimmte Kettenstrukturen spezifisch. Während Heparin in vitro gerinnungshemmend wirksam ist, zeigt der Vergleich der gerinnungshemmenden Wirkung in der Blutzirkulation mit der chemischen Konzentration im Blut, daß in vivo eine Aktivierung von nicht gerinnungshemmend aktiven Fraktionen bzw. Heparinketten erfolgt. Heparin wird rasch von den Zellen des RES-Systems gegen einen Konzentrationsgradienten aufgenommen, so daß in vivo die Heparinkonzentration im Gefäßendothel lOOOfach höher ist als im Blut.Die Fixierung des Heparins im Endothel vermehrt das elektronegative Potential des Endothels. Diese Wirkung und andere Wirkungen (die Aktivierung von Antithrombin III etc.) sind lokal die Basis der thromboseverhütenden Heparinwirkung. Demnach ist das Endothel das Zielorgan für Heparin.

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