题 目: Proteins Flex to Function: Roles of Conformational Plasticity in Protein Function
报告人: Professor Gaetano T. Montelione
Rensselaer Polytechnic Institute
时 间: 12月14日（周一）9:00-10:00
地 点: Online (Zoom会议)
会议 ID：627 9242 4126
主持人: 宋晨 研究员
Proteins, and their three-dimensional structures, are central to many aspects of biotechnology and medicine. However, our view of protein structure is biased by our crystallographic technology -- in which we study protein structures in crystal lattices. From a single high-resolution crystal structure, we often get only a part of the structure-function story. The true nature of a protein, like most organic molecules, is to adopt an ensemble, or Boltzmann distribution, of conformations. Sometimes this ensemble, which we call the “native protein structure”, is narrow (converged), and in the limit conforms to a crystallographic picture. In other cases, it is conformationally diverse. These conformational variants include surface sidechain and backbone loop conformers, multiple bound-state conformations of ligands, allosteric and enzyme transition states of the overall protein structure, and interdomain structural variability of multidomain proteins. These multiple conformational states underlie the structural “plasticity” of the protein, and often confer key biological functions. By improving our picture of these "native-state energy landscapes", we obtain a more complete and accurate understanding of the relationships between protein sequences, their structures, and their functions. Our recent efforts use molecular modeling and protein sequence co-variance analysis, together with experimental NMR, X-ray crystallography, and small angle X-ray scattering (SAXS) data, to gain insights into structure-function relationships of soluble and membrane proteins involved in virus infection, antibiotic resistance, and cancer biology. These studies also provide important starting points for understanding the roles of protein conformational landscapes in evolution, folding mechanisms, enzyme engineering, de novo protein design, and synthetic biology.
Gaetano Montelione is an expert and innovator in the fields of structural biology and protein NMR. Montelione is currently endowed chair in structural bioinformatics and professor of chemistry at the Rensselaer Polytechnic Institute. He carried out Ph.D. studies jointly with Profs. Harold Scheraga at Cornell University and Kurt Wüthrich at the ETH, Zurich, and postdoctoral studies with Prof. G. Wagner at Univ of Michigan. For many years he served as Director of the NIH Northeast Structural Genomics Consortium (NESG) (2000 – 2016) at Rutgers University, which developed a successful high-throughput pipeline for protein sample and 3D structure production. More than 1,300 structures were determined by the NESG team, lead by Montelione, using crystallography and NMR. Most of these were the first structures determined from large protein families, providing the basis for modeling of hundreds of thousands of homologous proteins. With Prof. G. Wagner, Montelione carried out pioneering work on triple-resonance NMR pulse sequence development. Montelione has made key contributions in computational NMR methods development, including the development of software for automated analysis of protein resonance assignments, automated analysis of 3D structures, and for protein NMR model quality assessment. The group’s biomedical focus areas include structure-function studies of proteins and complexes involved in cancer biology and influenza virus infection. Work with R. Krug on the influenza A non-structural protein 1 (NS1) has provided the basis for creation of attenuated virus vaccines. The lab’s current methodsdevelopment focus involves combining evolutionary sequence co-variance restraints from bioinformatics together with sparse NMR data to determine the 3D structures of challenging proteins, including membrane proteins associated with cancer biology. As an advisor to the world-wide Protein Data Bank, Montelione leads efforts to standardize methods for protein NMR model validation. Montelione is also a member of several academic and commercial structural biology advisory groups, co-chair of the international wwPDB Task Force on NMR Structure Validation, member of the Organizing Committee for the Critical Assessment of Protein Structure Prediction (CASP), and Foreign Expert Advisor in Protein Engineering to the Key Laboratory of Biotechnology at Jiangnan University, Wuxi, China.