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Updated: Jan 25, 2026
10:59
Enrichment of Bacterial Lipoproteins and Preparation of N-terminal Lipopeptides for Structural Determination by Mass Spectrometry
Published on: May 21, 2018
9.3K
Structure of lipoprotein lipase in complex with GPIHBP1
Rishi Arora1, Amitabh V Nimonkar2, Daniel Baird1
1Chemical Biology and Therapeutics, Novartis Institutes for Biomedical Research, Cambridge, MA 02139.
Summary
Researchers determined the first crystal structures of lipoprotein lipase (LPL) complexed with GPIHBP1. These structures reveal LPL can function as a monomer, challenging previous assumptions about its activity in triglyceride metabolism.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Metabolism
Background:
- Lipoprotein lipase (LPL) is crucial for triglyceride (TG) metabolism, hydrolyzing TGs in TG-rich lipoproteins (TRLs) to regulate circulating TG levels.
- Previous structural information for LPL was limited due to its instability, relying on homology models.
Purpose of the Study:
- To obtain and determine the high-resolution crystal structures of human LPL in complex with its accessory protein GPIHBP1.
- To elucidate the structural basis of LPL activity, stabilization, and transport by GPIHBP1.
- To investigate the oligomeric state of active LPL.
Main Methods:
- Coexpression of LPL with a soluble GPIHBP1 variant and chaperone LMF1 to form a stable complex.
- X-ray crystallography to determine the structure of the LPL/GPIHBP1 complex at 2.5-3.0 Å resolution.
- Structure determination of an LPL/GPIHBP1 complex with a novel inhibitor bound.
Main Results:
- The first crystal structures of human LPL complexed with human GPIHBP1 were obtained.
- A structure with a bound inhibitor revealed ordered lid and lipid-binding regions of LPL.
- Biochemical data and structures support LPL functioning as a monomeric 1:1 complex with GPIHBP1, challenging the established homodimer model.
Conclusions:
- The crystal structures provide unprecedented insight into the mechanism of LPL-mediated TRL lipolysis.
- GPIHBP1 plays a vital role in stabilizing and transporting LPL.
- LPL, when complexed with GPIHBP1, can be active as a monomer, revising our understanding of its functional state.
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