Skip to main content

NMR Studies of Human Apolipoprotein-E N-terminal Domain

EMSL Project ID


This research proposal is centered on NMR structural studies of human apolipoprotein-E (apoE). ApoE plays important roles in several human diseases, including atherosclerosis and Alzheimers diseases. We will particularly focus on solving the full-length apoE N-terminal domain, apoE(1-183). Although there is a X-ray crystal structure available for this domain, this structure only contains residue 23-166, whereas the rest of the regions have not yet been seen in the crystal structure. Recent experimental data indicates that several residues beyond region 23-166 are critical in apoE LDL receptor binding activity. These results indicate that more structural studies of the apoE N-terminal domain are required to resolve these problems. The X-ray crystal structure indicates that residues beyond 23-164, either at the N-terminus or the C-terminus, are flexible and have no observable electron density map in the X-ray diffraction. Thus, NMR structural studies of the apoE N-terminal domain may provides a possible solution to these issues. Further, preliminary experimental evidence suggests that apoE(1-183) provides the complete LDL receptor binding activity for apoE. We have 2H/15N/13C-triple labeled apoE(1-183) for 3D/4D heteronuclear NMR experiments. Our preliminary NMR studies indicated that apoE(1-183) adopted a similar helix-bundle structure at several different pHs, including pH6.4 and 3.2. Our NMR data further indicates the presence of NMR signals for those residues beyond 23-164 region, suggesting the possibility of a complete NMR assignment for intact apoE(1-183). In addition, this result also suggests that we may obtain a NMR structure of an intact apoE N-terminal domain in solution. We anticipate that a NMR structure of the intact apoE N-terminal domain may provide answers to the above important issues pertaining to the apoE LDL receptor binding activity.

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

Chen B, X Ren, T Neville, WG Jerome, DW Hoyt, DL Sparks, G Ren, and J Wang. 2009. "Apolipoprotein AI tertiary structures determine stability and phospholipid-binding activity of discoidal high-density lipoprotein particles of different sizes." Protein Science 18(5):921-935. doi:10.1002/pro.101
Xu C, A Sivashanmugam, DW Hoyt, and J Wang. 2005. "A Complete Backbone Assignment of the Apolipoprotein E LDL Receptor Binding Domain [Letter to the Editor]." Journal of Biomolecular NMR 32(2):177.