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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) and apoAI(1-209). 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 (Borhani et al, 1997), 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. Our preliminary data indicated that full-length apoA-I aggregate under NMR sample concentration (~ 1 mM), however, apoA-I(1-186) and apoAI(1-209) aggregate much less than full-length apoA-I (data not shown). We have worked out an experimental condition in which both apoA-I(1-186) and apoAI(1-209) are monomeric at ~1 mM concentration. Thus, we are in a good position to carry out a complete structural study of these two apoAI truncation mutants 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

Xuefeng Ren
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
Highly Oxidizing Excited States of Re and Tc Complexes
Luminescence from the trans-Dioxotechnetium(V) Chromophore