The molecular basis for the role of apolipoprotein A-II in cholesterol and triglyceride metabolism
EMSL Project ID
61052
Abstract
Apolipoprotein (apo)A-II is an abundant human plasma protein primarily in high-density lipoproteins (HDL) but also in very low density lipoproteins (VLDL) and chylomicrons. Despite a large literature, its physiological functions remain ambiguous and widely debated. For example, it has been postulated to play both beneficial and detrimental roles in cardiovascular disease (CVD) development. We believe that apoA-II functions quite differently than other apolipoproteins, which tend to act directly as a co-factor or ligand. Our work shows that apoA-II can stimulate HDL to promote cholesterol efflux from cells, but only when apoA-I is present. This is important because HDL cholesterol efflux proficiency is a better predictor of cardiovascular disease (CVD) than its plasma levels. We will define the mechanism for apoA-II’s potentiation of HDL-mediated cholesterol efflux by testing its effects on apoA-I structure using innovative structural techniques including cryo-electron microscopy.
Project Details
Project type
Cryo-EM Only
Start Date
2023-11-30
End Date
N/A
Status
Active
Released Data Link
Team
Principal Investigator
Team Members