Lei Zhang, Xi'an Jiaotong University
601, Pao Yue-Kong Library
The dynamic personalities and structural heterogeneities of soft-macromolecules are essential for understanding proper functions. Unfortunately dynamic/heterogeneous structural determination by traditional approaches such as X-ray crystallography and electron microscopy (EM) of single particle reconstruction is limited due to averaging thousands of different molecules, including those of different conformations. Cryo-electron tomography (cryoET) is a traditional approach to determine 3-dimensional (3D) reconstruction of a single soft-macromolecule. Recently, we developed serials of individual particle electron microscopy (EM) technologies, including different sample preparation protocols such as optimized negative-staining and cryo-positive staining, and “Focused Electron Tomography Reconstruction (FETR)” algorithm to improve the reconstruction resolution of a single-instance macromolecule. This method is not only free from an initial model and an average of multiple molecules, but also can tolerate certain levels of measuring tilt error. Since it can precisely determine structural details of a single molecule, it was named “Individual-Particle Electron Tomography (IPET)” method. IPET/FETR provides a new and robust approach to determine the structure of single-molecules and can be used to study the dynamic character and structural heterogeneity of macromolecules in many applications. So far, by employing this method, the dynamic structures and function of human antibodies, lipoproteins, and double-helix DNA had been studied.
 L. Zhang, J. Song, G. Cavigiolio, B. Ishida, S. L. Zhang, J. J. Wang, K. H. Weisgraber, H. J. Pownall, K-A. Rye, J. P. Kane, M. Oda, G. Ren, J. Lipid Res. 52(1), 175-184 (2011)
 L. Zhang, G. Ren, PLoS ONE 7(1), e30249 (2012)
 L. Zhang, F. Yan, S. L. Zhang, D. S. Lei, M. A. Charles, G. Cavigiolio, M. Oda, R. M. Krauss, K. H. Weisgraber, K-A. Rye, H. J. Pownall, X. Y. Qiu, G. Ren. Nat. Chem. Bio. 8, 342-349 (2012)
 X. Zhang, L. Zhang, H. M. Tong, B. Peng, M. J. Rames, S. L. Zhang, G. Ren, Sci. Rep. 5, 9803 (2015)
 L. Zhang, D. S. Lei, J. M. Smith, M. Zhang, H. M. Tong, X. Zhang, Z. Y. Lu, J. K. Liu, P. Alivisatos, G. Ren, Nat. Commun. 7, 11083 (2016)