Zhejiang University School of Medicine Discover

Prof. Xing Zhang Revealed the Structural Basis for the Stabilization of Cleaved rRNAs and Paromomyci

2016-11-02   |  

        Prof. Xing Zhang, director of the center of cryo electron microscopy, and his group revealed the structural basis for the stabilization of cleaved rRNAs and paromomycin specificity of Leishmania Donovani ribosome by determination and comparison of Leishmanialand human ribosomes. The results were published on Nature Communications (http://www.nature.com/articles/ncomms13223).

Leishmania Donovani is a protozoa pathogen, spread primarily by sand-fly bites, which causes ~0.4 million visceral leishmaniasis each year. Visceral leishmaniasis is life threatening without treatment and current available drugs are significant toxic. Moreover, resistant strains of Leishmania have been emerged, making it necessary to develop novel therapies to treat leishmaniasis. Ribosome, as the protein synthesis machine, is the major target for many antibiotics. Interestingly, the 28S rRNA of the Leishmania ribosome is cleaved into six separate fragments in contrast to a single 28S rRNA in most species including human, and these six rRNA fragments interact with each another and with unique protein extensions for structural integrity. Therefore, the group use cryoEM to determine atomic structures of ribosomes from both the Leishmania Donovani and human in order to reveal their structural differences. The structures elucidate the organization and structure of the six cleaved rRNA fragments and 71 proteins. Particularly, structural differences between the two ribosome structures at their decoding A-site explains how the bacterial ribosome-targeting drug paromomycin inhibits the eukaryotic Leishmania Donovani ribosome with minimal toxicity to human. Such structural information would provide insight into developing novel antibiotics against Leishmania Donovani.

VIEW MORE

Email: global_zusm@zju.edu.cn Fax:+86-571-88208022 TEL: +86-571-88208100 Address: 866 Yuhangtang Rd, Hangzhou 310058, P.R. China. ©2020 Zhejiang University School of Medicine. All Rights Reserved