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Region Hovedstaden - en del af Københavns Universitetshospital
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On the mechanism of angiopoietin-like protein 8 for control of lipoprotein lipase activity

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Expression and one-step purification of active LPL contemplated by biophysical considerations

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. ANGPTL4 sensitizes lipoprotein lipase to PCSK3 cleavage by catalyzing its unfolding

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Chylomicronemia from GPIHBP1 autoantibodies

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  4. ANGPTL4 inactivates lipoprotein lipase by catalyzing the irreversible unfolding of LPL's hydrolase domain

    Publikation: Bidrag til tidsskriftKommentar/debatForskningpeer review

  5. The structural basis for monoclonal antibody 5D2 binding to the tryptophan-rich loop of lipoprotein lipase

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. ANGPTL4: a new mode in the regulation of intravascular lipolysis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Expression and one-step purification of active LPL contemplated by biophysical considerations

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. The Urokinase Receptor (uPAR) as a "Trojan Horse" in Targeted Cancer Therapy: Challenges and Opportunities

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  4. The Importance of Lipoprotein Lipase Regulation in Atherosclerosis

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

Vis graf over relationer

Angiopoietin-like (ANGPTL) 8 is a secreted inhibitor of LPL, a key enzyme in plasma triglyceride metabolism. It was previously reported that ANGPTL8 requires another member of the ANGPTL family, ANGPTL3, to act on LPL. ANGPTL3, much like ANGPTL4, is a physiologically relevant regulator of LPL activity, which causes irreversible inactivation of the enzyme. Here, we show that ANGPTL8 can form complexes with either ANGPTL3 or ANGPTL4 when the proteins are refolded together from their denatured states. In contrast to the augmented inhibitory effect of the ANGPTL3/ ANGPTL8 complex on LPL activity, the ANGPTL4/ANGPTL8 complex is less active compared with ANGPTL4 alone. In our experiments, all three members of the ANGPTL family use the same mechanism to inactivate LPL, which involves dissociation of active dimeric LPL to monomers. This inactivation can be counteracted by the presence of glyco-sylphosphatidylinositol-anchored HDL binding protein 1, the endothelial LPL transport protein previously known to protect LPL from spontaneous and ANGPTL4-catalyzed inactivation. Our data demonstrate that ANGPTL8 may function as an important metabolic switch, by forming complexes with ANGPTL3, or with ANGPTL4, in order to direct the flow of energy from triglycerides in blood according to the needs of the body.

OriginalsprogEngelsk
TidsskriftJournal of Lipid Research
Vol/bind60
Udgave nummer4
Sider (fra-til)783-793
Antal sider11
ISSN0022-2275
DOI
StatusUdgivet - apr. 2019

ID: 56564932