题 目：Single-Molecule 3D Imaging for the Study of Protein Structure, Dynamics and Mechanism
报告人：Professor Gang Ren（任罡）
The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley CA 94720-8197
Proteins have the unique ability to function specifically and efficiently, which is attained through its three-dimensional (3D) structure, flexibility and conformational changing. However, the structural studies on proteins with large-scale flexibility, dynamics, and heterogeneity is challenged by current techniques, including X-ray crystallography, nuclear magnetic resonance spectrum, small angle scattering and cryo-electron microscopy (cryo-EM) 3D reconstruction. A fundamental solution to studying the flexible protein structure should be based on the structure determination of each individual protein molecule (without averaging from different protein molecules). Electron tomography (ET) provides a novel tool to image each individual molecule from a series of tilt angles at near atomic resolution. However, the signal obtained from an individual molecule is extremely weak due to radiation limitations. For decades, people believed it was impossible to use a single molecule to achieve 3D structure with a resolution that can be used to understand the protein dynamics and mechanisms. We re-investigated this possibility and proposed an approach, named individual-particle electron tomography (IPET) to improve the 3D structure resolution. This approach does not require a pre-given initial model or class averaging of multiple molecules, yet can achieve single-molecule 3D structure at 1-2 nm resolution from negative staining samples, and 3-4 nm from cryo-EM samples. Through the comparison of the 3D structures from different molecules, the approach provides a new opportunity to reveal the dynamic characteristics, equilibrium fluctuations, mechanisms, aggregations and even structural changes in proteins during chemical reactions or biological events.
Dr. Gang Ren, a career staff scientist and principal investigator at the Molecular Foundry, Lawrence Berkeley National Laboratory, USA. He received his BS in the department of theoretical physics at Lanzhou University in 1990. He received his MS training from Prof. Yishi Duan in same department in 1993. In 1997, he received PhD in the Profs. Ke-Shin Kuo and Lian-mao Peng’s groups, the material physics department at University of Science and Tech Beijing. In the same year, he joined Profs. Alok Mitra and Mark Yeager groups in the department of cell biology at The Scripps Research Institute, USA as a postdoctoral fellow in the field of cryo-EM, which was supported by American Heart Association and California Aids Research program. In 2003, he worked with Prof. Wah Chiu as a research associate in the National Center for Macromolecular Imaging (NCMI) at Baylor College of Medicine, Houston, TX. In 2006, he started his independent research laboratory as a Keck Fellow and assistant research biochemist in the Biochemistry and biophysics department at UCSF. In 2010, he moved to the Molecular Foundry at Lawrence Berkeley National Laboratory, Berkeley, CA. His research focused on protein dynamics by electron microscopy, which is supported by funds from US Department of Energy, NIH R01s and pharmaceutical companies. He published about 100 research papers in prestigious journals such as Nature Chemical Biology and PNAS. He serves as an editorial board member of scientific reports and associate director of CASSS.