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conferenceseries.com
Volume 10, Issue 8 (Suppl) J Proteomics Bioinform, an open access journal
ISSN: 0974-276X Structural Biology 2017
September 18-20, 2017
9th International Conference on
Structural Biology
September 18-20, 2017 Zurich, Switzerland
Andrei Korostelev, J Proteomics Bioinform 2017, 10:8(Suppl)
DOI: 10.4172/0974-276X-C1-0100
Conformational dynamics revealed by ensemble cryo-EM
Andrei Korostelev
UMass Medical School, USA
Virus propagation depends on efficient synthesis of viral proteins by the host translational machinery. Internal ribosome
entry sites (IRESs) of viral mRNAs mediate cap-independent initiation. Intergenic-region (IGR) IRESs of Dicistroviridae
family, which includes the Taura syndrome virus (TSV) and Cricket paralysis virus (CrPV), use the most streamlined
mechanism of initiation, independent of initiation factors and initiator tRNA. A tRNA-mRNA like pseudoknot of IGR IRESs
binds the ribosomal A (aminoacyl-tRNA) site of the 80S ribosome. The pseudoknot translocates to the P site to allow binding
of the first tRNA and initiate translation. Using electron cryo-microscopy of a single specimen, we resolved five ribosome
structures formed with the Taura syndrome virus IRES and translocase EEF2 GTP bound with sordarin. The structures suggest
a trajectory of IRES translocation, required for translation initiation, and provide an unprecedented view of eEF2 dynamics. The
IRES rearranges from extended to bent to extended conformations. This inchworm-like movement is coupled with ribosomal
inter-subunit rotation and 40S head swivel. eEF2, attached to the 60S subunit, slides along the rotating 40S subunit to enter
the A site. Its diphthamide-bearing tip at domain IV separates the tRNA-mRNA-like pseudoknot I (PKI) of the IRES from
the decoding center. This unlocks 40S domains, facilitating head swivel and biasing IRES translocation via hitherto-elusive
intermediates with PKI captured between the A and P sites.
Biography
Andrei Korostelev is passionate about mechanisms of translation regulation. He received PhD in Michael S Chapman laboratory at Florida State University in
2003 and performed Postdoctoral studies with Harry F Noller in 2004-2010. The Korostelev laboratory at the RNA Therapeutics Institute uses recent advances in
biochemical and structural methods to elucidate detailed mechanisms that govern translation and regulation of translation under stress conditions or during disease.
Recent work revealed high-resolution “frames” of the motions that the translational machinery undergoes during bacterial stress responses (including the stringent
response) and viral infection, as summarized on the laboratory web site: