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  English.dicp.cas.cn    Posted:2017-03-24
Watching Protein to Dance, an Integrative Approach

Time: Mar. 24, 2017 09:00 AM

Conference Room on the First Floor, Basic Energy Building

Chun Tang

CAS Key Laboratory of Magnetic Resonance in Biological Systems   

Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences

  A protein exists in multiple conformations in solution. The dynamic fluctuation among different conformational states enables the protein to perform its designed function, from molecular recognition to enzymatic catalysis. To visualize the protein dynamics, my laboratory utilizes both ensemble and single-molecule based methods. The ensemble-based methods include nuclear magnetic resonance (NMR), small-angle X-ray scattering (SAXS), and chemical cross-linking coupled with mass spectrometry (CXMS). Single-molecule fluorescence resonance energy transfer (smFRET) allows rapid determination of the number of conformational states present and the relative populations, which complements the ensemble-based method. In particular, we developed paramagnetic NMR methods to characterize protein dynamics, by attaching a paramagnetic probe site-specifically to a protein under investigation. Among the paramagnetic NMR techniques, paramagnetic relaxation enhancement (PRE) exhibits an distance dependence and is exquisitely sensitive to protein minor conformation. The paramagnetism from lanthanoid on the other hand, elicits pseudo-contact shift on protein nuclei and afford both vectoral and angular information about the protein. Both paramagnetic NMR and smFRET require site-specific attachment of an extrinsic probe, which is the observation for protein dynamics. However, conjugation of the probe mostly involves sulfhydryl chemistry, and such scheme may be a problem for cysteine-rich proteins. Recently, we developed a new paramagnetic probe that utilizes the orthogonal chemistry of an unnatural amino acid. A covalently attached probe may inadvertently perturb protein structure. To avoid this, we have also developed label-free paramagnetic NMR method. Together, such an integrative approach gives us better visualization of protein dynamics and the constituting conformational states.

Dr. Chun Tang is a senior investigator from the Chinese Academy of Sciences Wuhan Institute of Physics and Mathematics researcher. He obtained his BS degree from the Department of Biology of Zhejiang University in 1998, and obtained his PhD degree from the University of Maryland Baltimore Count under the mentorship of Prof. Michael Summers, member of the US National Academby of Sciences. From 2003 to 2007, he performed his postdotral research at the National Institutes of Health with US Academician Dr. G. Marius Clore. In 2008, he was appointed as assistant professor of biochemistry at the University of Missouri. He was selected as the "Hundred Talents Program" of the Chinese Academy of Sciences in 2010. He is currently the director of the Key Laboratory of Biomagnetic Resonance Analysis of the Chinese Academy of Sciences.

Professor Tang Chun has long been engaged in the research of the dynamic structural changes of protein and other biological macromolecules, and has developed a series of methods of nuclear magnetic, biophysical and computational methods, which are used to describe the molecular mechanism of the function of biological macromolecules such as proteins. Prof. Tang has published more than 50 articles in the world's leading publications or published more than 50 papers (3 of which are published in Nature journals, 2 published in Nature, 8 published in PNAS, JACS and Angew Chem Intl Ed ), The paper cited more than 2,000 times, many times invited at the domestic and international academic conference for the General Assembly report.

Tang Chun, a researcher of the National Natural Science Foundation of China, was selected by the Howard Hughes Medical Institute (HHMI) International Young Scientist Award. Now the Ministry of Science and Technology major scientific research program chief scientist, national "millions of talent project" selected. Also served as chairman of the Hubei Provincial Institute of Crystals, China Biomagnetic Resistors Professional Committee, Deputy Secretary-General, molecular biophysics, single molecular biophysics, biophysical chemistry professional committee.

 

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