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NMR Studies of Human Apolipoprotein-AI

EMSL Project ID


In this proposal, we plan to focus on determination of the NMR structure of lipid-free human apoA-I(1-186). ApoA-I is a 243-residue protein (28.1 kDa), which is the main protein component of HDL and binds to lipids. It also serves as a ligand of the HDL receptor SR-BI and an activator of LCAT, a key enzyme in reverse cholesterol transport. Unfortunately, there is not many structural studies reported to date for this important plasma protein. In 1997, a X-ray crystal structure of apoA-I(44-243) has been reported, however, this structure could not be used to explain structure/functional data of apoA-I. One of the difficult for structural study of apoA-I is that this protein aggregates at low concentration that resists to crystallization. Therefore, we propose to determine the structure of apoA-I using NMR techniques. We currently focus on NMR studies of apoA-I(1-186). We have worked out an experimental condition in which apoA-I(1-186) is monomeric at ~1 mM concentration. Thus, we are in a good position to carry out a complete structural study of apoA-I(1-186) using NMR techniques. We believe that this study will serve as a first step of NMR studies of full-length apoA-I. We anticipate that the structures of human apoA-I will help us understand how apoA-I recruits lipids to initiate HDL formation and how apoA-I promotes HDL to recruit more neutral lipids, two central roles played by apoA-I in reverse cholesterol transport. Since a low level of plasma HDL and a compromised HDL function are the common thread of metabolic disorders/diseases including: atherosclerosis, diabetes, obesity, stroke, and Alzheimer's diseases, the results obtained from this proposal should have significant implications for the intervention of new medicine to treat these metabolic disorders/diseases.

Project Details

Project type
Capability Research
Start Date
End Date


Principal Investigator

Jianjun Wang
Wayne State University

Team Members

So-Young Shin
Wayne State University

Jianglei Chen
Wayne State University

Bin Chen
Wayne State University

Related Publications

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