Binding of hepatic lipase to heparin: identification of specific heparin-binding residues in two distinct positive charge clusters

Sendak, Rebecca A.; Berryman, Darlene E.; Gellman, Gabrielle; Melford, Kristan; Bensadoun, André

doi:10.1016/s0022-2275(20)32060-5

Cited by 22 publications

(2 citation statements)

References 41 publications

(62 reference statements)

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“…Like LPL and HL, EL also functions in the plasma compartment, and our initial report showed that overexpression of EL in mice profoundly altered plasma lipoprotein levels. The putative heparin-binding (6)(7)(8) and hydrophobic regions implicated in lipid or lipoprotein binding (9)(10)(11)(12) that are present in LPL and HL are highly conserved in EL, suggesting that EL, like LPL and HL, is anchored to the luminal endothelial surface via heparan sulfate proteoglycans where it can interact directly with lipoproteins. Initial reports indicated that EL had phospholipase activity (4,5) but the enzymatic activity was not characterized further.…”

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confidence: 99%

Characterization of the lipolytic activity of endothelial lipase

McCoy

Sun

Marchadier

et al. 2002

Journal of Lipid Research

284

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Endothelial lipase (EL) is a new member of the triglyceride lipase gene family previously reported to have phospholipase activity. Using radiolabeled lipid substrates, we characterized the lipolytic activity of this enzyme in comparison to lipoprotein lipase (LPL) and hepatic lipase (HL) using conditioned medium from cells infected with recombinant adenoviruses encoding each of the enzymes. In the absence of serum, EL had clearly detectable triglyceride lipase activity. Both the triglyceride lipase and phospholipase activities of EL were inhibited in a dose-dependent fashion by the addition of serum. The ratio of triglyceride lipase to phospholipase activity of EL was 0.65, compared with ratios of 24.1 for HL and 139.9 for LPL, placing EL at the opposite end of the lipolytic spectrum from LPL. Neither lipase activity of EL was influenced by the addition of apolipoprotein C-II (apoC-II), indicating that EL, like HL, does not require apoC-II for activation. Like LPL but not HL, both lipase activities of EL were inhibited by 1 M NaCl. The relative ability of EL, versus HL and LPL, to hydrolyze lipids in isolated lipoprotein fractions was also examined using generation of FFAs as an end point.As expected, based on the relative triglyceride lipase activities of the three enzymes, the triglyceride-rich lipoproteins, chylomicrons, VLDL, and IDL, were efficiently hydrolyzed by LPL and HL. EL hydrolyzed HDL more efficiently than the other lipoprotein fractions, and LDL was a poor substrate for all of the enzymes.

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confidence: 99%

Characterization of the lipolytic activity of endothelial lipase

McCoy

Sun

Marchadier

et al. 2002

Journal of Lipid Research

284

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“…We note that this behavior is in stark contrast to previously observed shifts in the concentration of salt required for elution of other mutated extracellular proteins from heparin-Sepharose. Fibroblast growth factors FGF1, FGF2 and hepatic lipase, for example, bind very distinct modifications of HS by modification-specific interactions, and interferon-γ and interleukin-8 bind HS by domain-specific interactions (Thompson et al, 1994;Wong et al, 1995;Sendak et al, 2000). As a consequence, mutagenesis of basic amino acids in these proteins reduce the relative amounts of NaCl required to elute the proteins from the column.…”

Section: Positively Charged Shh Amino Acids Interact With Hs and Heparinmentioning

confidence: 99%

Drosophila hedgehog signaling range and robustness depend on direct and sustained heparan sulfate interactions

Manikowski

Steffes

Froese

et al. 2023

Front. Mol. Biosci.

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Morphogens determine cellular differentiation in many developing tissues in a concentration dependent manner. As a central model for gradient formation during animal development, Hedgehog (Hh) morphogens spread away from their source to direct growth and pattern formation in the Drosophila wing disc. Although heparan sulfate (HS) expression in the disc is essential for this process, it is not known whether HS regulates Hh signaling and spread in a direct or in an indirect manner. To answer this question, we systematically screened two composite Hh binding areas for HS in vitro and expressed mutated proteins in the Drosophila wing disc. We found that selectively impaired HS binding of the second site reduced Hh signaling close to the source and caused striking wing mispatterning phenotypes more distant from the source. These observations suggest that HS constrains Hh to the wing disc epithelium in a direct manner, and that interfering with this constriction converts Hh into freely diffusing forms with altered signaling ranges and impaired gradient robustness.

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An α-Helical Domain within the Carboxyl Terminus of Herpes Simplex Virus Type 1 (HSV-1) glycoprotein B (gB) is Associated with Cell Fusion and Resistance to Heparin Inhibition of Cell Fusion

Foster

Melancon²,

Kousoulas³

2001

Virology

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Previous studies from our laboratory indicated that a 28-amino-acid carboxyl-terminal truncation of gB caused extensive virus-induced cell fusion (Baghian et al., 1993, J Virol 67, 2396-2401). We tested the ability of additional truncations and mutations within gB to cause cell fusion in the recently established virus-free cell fusion assay (Turner et al., 1998, J. Virol. 72, 873-875). Deletion of the carboxyl-terminal 28 amino acids of gB (gBDelta28), which removed part of the predicted alpha-helical structure H17b, caused extensive cell fusion. A gB truncation specified by gBDelta36, which removed the entire H17b domain, caused as much cell fusion as the gBDelta28 truncation. Similarly, gB(A874P) containing a substitution of an Ala with Pro within H17b caused cell fusion. Heparin, a gB-specific inhibitor of virus-induced cell fusion, inhibited both wild-type gB and gB(syn3)-mediated cell fusion. In contrast, fusion of cells transfected with gB(Delta28), gB(Delta36), or gB(A874P) was resistant to heparin inhibition of cell fusion. We concluded the following: (1) The predicted alpha-helical structure of H17b within the carboxyl terminus of gB is involved in both virus-induced and virus-free cell fusion. (2) Heparin is a specific inhibitor of gB-mediated fusion in both systems. (3) Resistance to heparin inhibition of gB-mediated cell fusion is associated with the predicted alpha-helical structure H17b within the carboxyl terminus of gB.

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Binding of hepatic lipase to heparin: identification of specific heparin-binding residues in two distinct positive charge clusters

Cited by 22 publications

References 41 publications

Characterization of the lipolytic activity of endothelial lipase

Characterization of the lipolytic activity of endothelial lipase

Drosophila hedgehog signaling range and robustness depend on direct and sustained heparan sulfate interactions

An α-Helical Domain within the Carboxyl Terminus of Herpes Simplex Virus Type 1 (HSV-1) glycoprotein B (gB) is Associated with Cell Fusion and Resistance to Heparin Inhibition of Cell Fusion

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