Structural Biology

Biography

Biography: Gang Ren

Abstract

Proteins 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 proteins 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 microsc opy    (EM) single-particle reconstruction. A fundamental approach to study the structure of flexible proteins should be based on the signal from each individual protein molecule itself instead of averaging fr om different protein molecules. EM provide 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 protein molecule. Through the structure determination of each individual molecule, the compar ison of these molecular structures provides a new opportunity to reveal the dynamic character, equilibrium fluctuation, mechanism, aggregation and even structural changes in proteins during a chemical reaction or biological event.