Title :
structure of the lipoprotein lipase-
GPIHBP1 complex that mediates plasma triglyceride hydrolysis
Abstract :
- Lipoprotein lipase ( LPL ) is responsible for the intravascular processing of triglyceride-rich lipoproteins
- The LPL within capillaries is bound to GPIHBP1 , an endothelial cell protein with a three-fingered LU domain and an N-terminal intrinsically disordered acidic domain
- Loss-of-function mutations in LPL or GPIHBP1 cause severe hypertriglyceridemia (chylomicronemia), but structures for LPL and GPIHBP1 have remained elusive
- Inspired by our recent discovery that GPIHBP1 's acidic domain preserves LPL structure and activity, we crystallized an LPL- GPIHBP1 complex and solved its structure
- GPIHBP1 's LU domain binds to LPL 's C-terminal domain, largely by hydrophobic interactions
- Analysis of electrostatic surfaces revealed that LPL contains a large basic patch spanning its N- and C-terminal domains
- GPIHBP1 's acidic domain was not defined in the electron density map but was position ed to interact with LPL 's large basic patch, providing a likely explanation for how GPIHBP1 stabilizes LPL
- The LPL- GPIHBP1 structure provides insights into mutations causing chylomicronemia