Heat Shock Protein 60 Is a High-Affinity High-Density Lipoprotein Binding Protein

2000 ◽  
Vol 277 (1) ◽  
pp. 228-235 ◽  
Author(s):  
Alexander V. Bocharov ◽  
Tatyana G. Vishnyakova ◽  
Irina N. Baranova ◽  
Alan T. Remaley ◽  
Amy P. Patterson ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
High Density Lipoprotein ◽  
Binding Protein ◽  
Density Lipoprotein ◽  
High Density ◽  
Heat Shock Protein 60 ◽  
High Affinity ◽  
Lipoprotein Binding

Characterization of a 95 kDa High Affinity Human High Density Lipoprotein-Binding Protein†

Biochemistry ◽  
2001 ◽  
Vol 40 (14) ◽  
pp. 4407-4416 ◽  
Author(s):  
Alexander V. Bocharov ◽  
Tatiana G. Vishnyakova ◽  
Irina N. Baranova ◽  
Amy P. Patterson ◽  
Thomas L. Eggerman
Keyword(s):  
High Density Lipoprotein ◽  
Binding Protein ◽  
Density Lipoprotein ◽  
High Density ◽  
High Affinity ◽  
Human High Density Lipoprotein ◽  
Lipoprotein Binding

scholarly journals A lipoprotein lipase–GPI-anchored high-density lipoprotein–binding protein 1 fusion lowers triglycerides in mice: Implications for managing familial chylomicronemia syndrome

2019 ◽  
Vol 295 (10) ◽  
pp. 2900-2912 ◽  
Author(s):  
Amitabh V. Nimonkar ◽  
Stephen Weldon ◽  
Kevin Godbout ◽  
Darrell Panza ◽  
Susan Hanrahan ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Enzyme Replacement Therapy ◽  
High Density Lipoprotein ◽  
Replacement Therapy ◽  
Lipoprotein Lipase ◽  
Binding Protein ◽  
Density Lipoprotein ◽  
High Density ◽  
Enzyme Replacement ◽  
Lipoprotein Binding

Lipoprotein lipase (LPL) is central to triglyceride metabolism. Severely compromised LPL activity causes familial chylomicronemia syndrome (FCS), which is associated with very high plasma triglyceride levels and increased risk of life-threatening pancreatitis. Currently, no approved pharmacological intervention can acutely lower plasma triglycerides in FCS. Low yield, high aggregation, and poor stability of recombinant LPL have thus far prevented development of enzyme replacement therapy. Recently, we showed that LPL monomers form 1:1 complexes with the LPL transporter glycosylphosphatidylinositol-anchored high-density lipoprotein–binding protein 1 (GPIHBP1) and solved the structure of the complex. In the present work, we further characterized the monomeric LPL/GPIHBP1 complex and its derivative, the LPL–GPIHBP1 fusion protein, with the goal of contributing to the development of an LPL enzyme replacement therapy. Fusion of LPL to GPIHBP1 increased yields of recombinant LPL, prevented LPL aggregation, stabilized LPL against spontaneous inactivation, and made it resistant to inactivation by the LPL antagonists angiopoietin-like protein 3 (ANGPTL3) or ANGPTL4. The high stability of the fusion protein enabled us to identify LPL amino acids that interact with ANGPTL4. Additionally, the LPL–GPIHBP1 fusion protein exhibited high enzyme activity in in vitro assays. Importantly, both intravenous and subcutaneous administrations of the fusion protein lowered triglycerides in several mouse strains without causing adverse effects. These results indicate that the LPL–GPIHBP1 fusion protein has potential for use as a therapeutic for managing FCS.

scholarly journals Glycosylphosphatidylinositol-Anchored High-Density Lipoprotein-Binding Protein 1 Plays a Critical Role in the Lipolytic Processing of Chylomicrons

2007 ◽  
Vol 5 (4) ◽  
pp. 279-291 ◽  
Author(s):  
Anne P. Beigneux ◽  
Brandon S.J. Davies ◽  
Peter Gin ◽  
Michael M. Weinstein ◽  
Emily Farber ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Binding Protein ◽  
Critical Role ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Binding
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