Principal Investigator, Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences.

Postdoctoral Fellow, The Rockefeller University, 2015-2021

Ph.D., Tsinghua University, 2010-2015

B.S., Sichuan University, 2006-2010

Professor Yixiao Zhang’s long-term passion is to use single-particle cryo-EM to answer challenging mechanistic questions. Biological macromolecules are of fundamental importance for cell physiology. Studies aimed at elucidating the mechanisms underlying the biological functions of these biomacromolecules are thus key to our­­­ understanding of basic biological processes and how their dysfunction results in disease. The goal of structural biology is to visualize the architecture of biomacromolecules and to establish the molecular basis that enables them to perform their functions. 

While there has been tremendous progress in the use of single-particle Cryo-EM for structure determination, limitations and challenges remain. For example, it can be difficult to recapitulate the appropriate physiological environment for a protein and it can be exquisitely difficult to resolve the conformation of an underrepresented class of molecules in a structurally heterogeneous population. These issues impede the structural study of many important biomacromolecules. Professor Zhang has developed novel methods to mimic membrane tension to study mechanosensitive ion channels, and overcame numerous challenges on diverse biological samples, ranging from membrane proteins, protein-protein complexes, protein-RNA complexes to intact virus. These investigations elucidated several exciting and long-awaited functional mechanisms and resulted in several papers in top-tier journals, including Nature, Science, Molecular Cell, Nature Structural & Molecular Biology, Nature Communications, and PNAS.  

Currently Professor Zhang’s group is working on (1) mammalian mechanosensitive channels to understand the human sensations and other biological processes stimulated by mechanical force. (2) the machineries that involved in neurodegeneration and other diseases to understand their molecular mechanisms. (3) the biological processes that govern X-chromosome inactivation.

Selected publications

1.      Zhang, Y., Daday, C., Gu, R., Cox, C.D., Martinac, B., Groot, B., Walz, T. (2021). Visualizing the mechanosensitive ion channel MscS under membrane tension. Nature, 590, 509-514.

2.      Dan, J.*, Zhang, Y.*, Lee, C.H., Valencia-Sanchez, M., Zhang, J., Wang, M., Holder, M., Svetlov, V., Tan, D., Nudler, E., Reinberg, D., Walz, T., Armache, K. (2021). Structures of monomeric and dimeric PRC:EZH1 reveal flexible modules involved in chromatin compaction. Nature Communications, 12(1): 714.

3.      Sun, Y.*, Zhang, Y.*, Aik, W.S., Yang, X.-C., Marzluff, W.F., Walz, T., Dominski, Z., and Tong, L. (2020). Structure of an active human histone pre-mRNA 3’-end processing machinery. Science 367, 700-703.

4.      Zhang, Y.*, Sun, Y.*, Shi, Y., Walz, T., and Tong, L. (2020). Structural Insights into the Human Pre-mRNA 3’-End Processing Machinery. Molecular Cell 77: 800-809.

5.      Su, M.*, Zhu, L.*, Zhang, Y.*, Paknejad, N.*, Dey, R., Huang, J., Lee, M.Y., Williams, D., Jordan, K.D., Eng, E.T., Ernst, O.P., Meyerson, J., Hite, R., Walz, T., Liu, W., Huang, X. (2020). Structural basis of the activation of heterotrimeric Gs-protein by isoproterenol-bound b1-adrenergic receptor. Molecular Cell 80:59-71.

6.      Nešić, D.*, Zhang, Y.*, Spasic, A.*, Li, J.*, Provasi, D., Filizola, M., Walz, T., and Coller, B.S. (2020). Cryo-Electron Microscopy Structure of the αIIbβ3-Abciximab Complex. Arteriosclerosis, Thrombosis, and Vascular Biology. 119.313671.

7.      Yu, J.*, Zhang, B.*, Zhang, Y.*, Xu, C.Q., Zhuo, W., Ge, J., Li, J., Gao, N., Li, Y., and Yang, M. (2018). A binding-block ion selective mechanism revealed by a Na/K selective channel. Protein & Cell 9, 629-639.

8.      Lees, J.A.*, Zhang, Y.*, Oh, M.S., Schauder, C.M., Yu, X., Baskin, J.M., Dobbs, K., Notarangelo, L.D., De Camilli, P., Walz, T., Renisch, K. (2017). Architecture of the human PI4KIIIalpha lipid kinase complex. Proc Natl Acad Sci. U.S.A 114, 13720-13725.

9.      Sun, Y.*, Zhang, Y.*, Hamilton, K., Manley, J.L., Shi, Y., Walz, T., and Tong, L. (2017). Molecular basis for the recognition of the human AAUAAA polyadenylation signal. Proc Natl Acad Sci. U.S.A 115, E1419-E1428.

10.  Zhang, Y., Ma, C., Yuan, Y., Zhu, J., Li, N., Chen, C., Wu, S., Yu, L., Lei, J., and Gao, N. (2014). Structural basis for interaction of a cotranslational chaperone with the eukaryotic ribosome. Nature Structural & Molecular Biology 21, 1042-1046.

11.  Wu, S., Tutuncuoglu, B., Yan, K., Brown, H., Zhang, Y., Tan, D., Gamalinda, M., Yuan, Y., Li, Z., Jakovljevic, J., et al. (2016). Diverse roles of assembly factors revealed by structures of late nuclear pre-60S ribosomes. Nature 534, 133-137.

Li, N., Zhai, Y., Zhang, Y., Li, W., Yang, M., Lei, J., Tye, B.K., and Gao, N. (2015). Structure of the eukaryotic MCM complex at 3.8 A. Nature 524, 186-191.