Contact

  • Title: Professor
  • Department: Institute of Biophysics
  • Address: Rm. 207 Lanzhou University School of Life Sciences
  • Tel: +86 13919048629
  • Fax:
  • Email: zwh@lzu.edu.cn
  • Homepage:
Bio

Wenhua Zhang recieved his 2014 Ph.D in Structural Biology with H. van Tilbeurgh from Université Paris-Sud 11, Orsay, France. Upon completing 3 years and half postdoctoral studies with J. Cherfils in French CNRS, Paris, France, he joined Lanzhou University School of Life Sciences, Lanzhou, China.

The Zhang laboratory studies the biosynthesis and cellular roles of tRNA N6-threonylcarbamoyladenosine (t6A), which is a necessary post-transcriptional modification universally found in ANN-decoding tRNAs in the three domains of life. The t6A is located 3'-adjacent to the anticodon triplet in the anticodon stem loop of tRNAs, wherein it plays pivotal roles in preventing the U33 and A37 from unwanted Watson-Crick pairing as well as in enhancing the base pairing between anticodon triplet from tRNA and codon triplet from mRNA. The absence or interfered making of tRNA t6A gravely affects cellular proteostasis and causes cell death, is also implicated in the growth and development of higher eukaryotes, and a set of human diseases,i.e. Galloway-Mowat Syndrome. The two last universal common ancestor (LUCA) families TsaC/Sua5 and TsaD/Kae1/Qri7 form a minimal duet to catalyze the substrates of L-threonine, Bicarbonate, ATP and tRNA to make tRNA t6A, during which a short-lived intermediate L-threonylcarbamoyladenylate (TC-AMP) is necessarily generated to couple the chemical transformations. However, the molecular mechanisms and machinery workings underlying tRNA t6A biosynthesis might vary among different life systems, as additional organism-specific enzymes are needed for the enzymatic reconstitution of tRNA t6A. The enzymes function in ensemble, namely protein complex, either stable or dynamic. His lab people are doggedly focused on analyzing the structure-function relationship of these ancient enzymes, and on elucidating the sequential assembly and regulatory layers of the tRNA t6A biosynthetic machinery as well. Furthermore, we are exploring the possible novel functions of KEOPS complex and the cellular implications of tRNA t6A and other important t6A derivative modifications (i.e. ht6A, m6t6A, ms2t6A, ct6A, ms2ct6A) pathway by applying an array of approaches and techniques in molecular biology, enzymology, structural biology, cellular biology and genetics.

Academic Appointments
Honors & Awards
Funding
Publications
  1. Wang, J., Zhou, J., Mao, X., Zhou, L., Chen, M., Zhang, W., Wang, E. and Zhou, X. (2022) Commonality and diversity in tRNA substrate recognition in t6A biogenesis by eukaryotic KEOPSs, Nucleic Acids Res., 50, 2223–2239.
  2. Galicia, C., Lhospice, S., Varela, P., Trapani, S., Zhang, W., Navaza, J., Herrou, J., Mignot, T. and Cherfils, J., (2019) MglA functions as a three-state GTPase to control movement reversals of Myxococcus xanthus. Nature Communications, 10, 5300.
  3. Das, S., Malaby, A., Nawrotek, A., Zhang,W., Zeghouf, M., Maslen, S., Skehel, M., Chakravarthy, S., Irving, T., Bilsel, O., Cherfils J. and Lambright, D. (2019) Structural Organization and Dynamics of Homodimeric Cytohesin Family Arf GTPase Exchange Factors in Solution and on Membranes. Structure27, 1782–1797.
  4. Missoury, S., Plancqueel, S., Gallay, I., Zhang, W., Liger, D., Durand, D., Dammak, R., Collinet, B. and van Tilbeurgh, H. (2018) The crystal structure of the bacterial TsaB/TsaD/TsaE complex responsible for the essential t6A tRNA-modification. Nucleic Acids Res., 46, 5850-5860.
  5. Pichard-Kostuch A.*, Zhang, W.*,  Liger, D., Daugeron, M., Letoquart, J.,  Gallay, I.,  Forterre, P., Collinet, B.,  van Tilbeurgh, H., Basta, T. (2018) Structure-function analysis of Sua5 protein reveals novel functional motifs required for the biosynthesis of the universal tRNA t6ARNA24, 926-938.
  6. Ferrandez, Y.*, Zhang, W.*, Peuroi, F., Akendengué, L., Blangy, A., Zeghouf, M. and Cherfils, J. (2017) Allosteric inhibition of the guanine nucleotide exchange factor DOCK5 by a small molecule. Scientific Reports, 7:14409| DOI:10.1038/s41598-017-13619-2|1-13
  7. Zhang, W., Collinet, B., Perrochia, L., Durand, D. and van Tilbeurgh, H. (2015) The ATP-mediated formation of the YgjD-YeaZ-YjeE complex is required for the biosynthesis of tRNA t6A in Escherichia coli. Nucleic Acids Res.43, 1804-1817.
  8. Zhang, W., Collinet, B., Graille, M., Daugeron, M.C., Lazar, N., Libri, D., Durand, D. and van Tilbeurgh, H. (2015) Crystal structures of the Gon7/Pcc1 and Bud32/Cgi121 complexes provide a model for the complete yeast KEOPS complex. Nucleic Acids Res.43, 3358-3372.
  9. Perrochia, L., Crozat, E., Hecker, A., Zhang, W., Bareille, J., Collinet, B., van Tilbeurgh, H., Forterre, P. and Basta, T. (2013) In vitro biosynthesis of a universal t6A tRNA modification in Archaea and Eukarya. Nucleic Acids Res.41, 1953-1964.
  10. He, J., Shi, J., Xu, X., Zhang, W., Wang, Y., Chen, X., Du, Y., Zhu, N., Zhang, J., Wang, Q. et al. (2012) STAT3 mutations correlated with hyper-IgE syndrome lead to blockage of IL-6/STAT3 signalling pathway. Journal of Biosciences37, 243-257.
  11. Jiang, P., Xu, X., Chen, Y., Zhang, W., Serradji, N., Yang, J., Dong, C. and Wang, Q. (2010) PMS-1077, a PAF antagonist, induced differentiation of HL-60 cells with its novel activity. Cell Biology International34, 1227-1230.
  12. Zhang, W., Lv, M., Hai, J., Wang, Q. and Wang, Q. (2010) Dicranostigma leptopodum (maxim) fedde induced apoptosis in SMMC-7721 human hepatoma cells and inhibited tumor growth in mice. Natural Science, 2, 457-463.
  13. Zhang, W., Yang, Y., Lin, C. and Wang, Q. (2010) Antioxidant attenuation of ROS-involved cytotoxicity induced by Paraquat on HL-60 cells. Health2, 235-261.
Latest Time:2022-10-19