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Title | Structure of dimeric lipoprotein lipase reveals a pore adjacent to the active site. |
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Journal, issue, pages | Nat Commun, Vol. 14, Issue 1, Page 2569, Year 2023 |
Publish date | May 4, 2023 |
![]() | Kathryn H Gunn / Saskia B Neher / ![]() |
PubMed Abstract | Lipoprotein lipase (LPL) hydrolyzes triglycerides from circulating lipoproteins, releasing free fatty acids. Active LPL is needed to prevent hypertriglyceridemia, which is a risk factor for ...Lipoprotein lipase (LPL) hydrolyzes triglycerides from circulating lipoproteins, releasing free fatty acids. Active LPL is needed to prevent hypertriglyceridemia, which is a risk factor for cardiovascular disease (CVD). Using cryogenic electron microscopy (cryoEM), we determined the structure of an active LPL dimer at 3.9 Å resolution. This structure reveals an open hydrophobic pore adjacent to the active site residues. Using modeling, we demonstrate that this pore can accommodate an acyl chain from a triglyceride. Known LPL mutations that lead to hypertriglyceridemia localize to the end of the pore and cause defective substrate hydrolysis. The pore may provide additional substrate specificity and/or allow unidirectional acyl chain release from LPL. This structure also revises previous models on how LPL dimerizes, revealing a C-terminal to C-terminal interface. We hypothesize that this active C-terminal to C-terminal conformation is adopted by LPL when associated with lipoproteins in capillaries. |
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Methods | EM (single particle) |
Resolution | 3.9 Å |
Structure data | EMDB-28554, PDB-8erl: |
Source |
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![]() | HYDROLASE / Dimer / lipase |