Structural Studies of Apolipoprotein A-I/preb-HDL Particles
EMSL Project ID
7791
Abstract
Cholesterol is a lipid that is necessary for our body. Only those cholesterol molecules that are in excess in the peripheral cells and blood vessels are the ?bad cholesterol? and need to be transport by the HDL particles to the liver for clearance. The reverse cholesterol transport pathway or the HDL pathway is the major drug target for several major human diseases, including heart disease, diabetes and Alzheimer?s disease. Apolipoprotein A-I (apoAI) is a 243-residue exchangeable apolipoprotein which is the most abundant protein component in HDL (~70%). Depending on the extent of lipidation, apoAI displays a dramatic conformational plasticity and may adopt one of four distinct conformations, including: (1). Lipid-free apoAI conformation (for specific phospholipid-binding). (2). ApoAI on preb-HDL (for specific cholesterol-binding). (3). ApoAI on discoidal HDL (for specific LCAT activation). (4). ApoAI on spherical HDL (for specific HDL-receptor binding). The conformational plasticity indeed enables apoAI to display multiple functions which regulate/direct HDL formation, maturation, transport and metabolism. ApoAI structures at different stages will be critical for our understanding of how HDL is formed, to become mature and then transported into the liver. This knowledge is indeed necessary in designing drugs that target the clearance of the ?bad cholesterol?. This proposal is aimed at solving one of the apoAI conformations, the apoAI/prebHDL conformation.
Project Details
Project type
Capability Research
Start Date
2004-06-01
End Date
2006-06-04
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
A complete backbone spectral assignment of human apolipoprotein AI on a 38 kDa preβHDL (Lp1-AI) particle Xuefeng Ren, Yunhuang Yang, Tracey Neville, David Hoyt, Daniel Sparks, Jianjun Wang
Apolipoprotein AI tertiary structures determine stability and phospholipidbinding activity of discoidal high-density lipoprotein particles of different sizes
Bin Chen, Xuefeng Ren, Tracey Neville, Gray Jerome, David W. Hoyt, Daniel Sparks, Gang Ren, and Jianjun Wang
Received 14 November 2008; Revised 25 February 2009; Accepted 26 February 2009
DOI: 10.1002/pro.101 Published online 16 March 2009 proteinscience.org
Kaiser NK, G Skulason, CR Weisbrod, S Wu, K Zhang, DC Prior, MA Buschbach, GA Anderson, and JE Bruce. 2008. "Restrained Ion Population Transfer: A Novel Ion Transfer Method for Mass Spectrometry." Rapid Communications in Mass Spectrometry 22(12):1955-1964.
Xie C, Y Chen, MH Engelhard, and C Song. 2012. "Comparative Study on the Sulfur Tolerance and Carbon Resistance of Supported Noble Metal Catalysts in Steam Reforming of Liquid Hydrocarbon Fuel." ACS Catalysis.