Individual-Particle Electron Tomography (IPET): a novel single-molecule approach to study the structure, dynamics, mechanism, and aggregation of flexible macromolecules
讲座名称：
Individual-Particle Electron Tomography (IPET): a novel single-molecule approach to study the structure, dynamics, mechanism, and aggregation of flexible macromolecules
讲座时间：
2015-09-18
讲座人：
任罡
形式：
校区：
兴庆校区
实践学分：
讲座内容：
报告题目：Individual-Particle Electron Tomography (IPET): a novel single-molecule approach to study the structure, dynamics, mechanism, and aggregation of flexible macromolecules
报 告 人：任罡 博士，职业科学家（Lawrence Berkeley National Laboratory, USA）
报告时间：9月18日（星期五）下午4：30-5：30
报告地点：中一楼3113
摘 要：
Macromolecules have the unique ability to function specifically and efficiently, which is attained through its three-dimensional (3D) structures and flexibility, as well as necessary conformational changes. However, structural study on macromolecules that have large-scale flexibility, dynamics, and heterogeneity is challenging by current techniques, including X-ray crystallography, nuclear magnetic resonance (NMR) spectrum, small angle scattering (SAXS) and electron microscopy (EM) single-particle reconstruction. The common modality of these techniques in determining the structure rely on the “signal” averaged from thousands to millions of different molecules under an assumption that the macromolecules remain in one or few identical conformations (no continuously changing conformation). Although this assumption works for some rigid-body molecules, for many macromolecules that are naturally soft and flexible, such as DNA, lipoproteins and antibodies, this assumption can have serious consequences.
A fundamental approach to study the structure of flexible macromolecules should be based on the signal from each individual molecule itself instead of averaging from different macromolecules. EM provides a novel tool to image each individual molecule at atomic resolution level; while electron tomography (ET) provide an approach to image a targeted molecule from a series of tilt angles. Although the signal obtained from an individual molecule has been believed for decades to be too weak to achieve any 3D structure with a meaningful resolution, we recently re-investigated this possibility carefully and proposed an individual-particle electron tomography (IPET) approach with a ‘‘focused electron tomography reconstruction’’ (FETR) algorithm to improve the 3D structure resolution via decreasing the reconstructing image size with an iterative refinement process. IPET does not require a pre-given initial model, class averaging of multiple molecules or an extended ordered lattice, but can provide near one nanometer resolution 3D structure from an individual macromolecule. Through the structure determination of each individual molecule, the comparison of these molecular structures provides a new opportunity to reveal the dynamic character, equilibrium fluctuation, mechanism, aggregation and even structural changes during a chemical reaction or biological event.
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