TCBG Seminar

Antibiotic Inhibition of the Universal Translator, the Ribosome

Professor Jamie Cate
Departments of Chemistry and MCB
University of California, Berkeley
Berkeley, CA

Monday, December 8, 2008
3:00 pm (CT)
3269 Beckman Institute


The ribosome is the universally conserved cellular machine that translates the genetic code into proteins. In bacteria, the ribosome is targeted by numerous antibiotics, which affect many steps in protein synthesis. We have been studying antibiotics that inhibit the processes of mRNA and tRNA translocation on the ribosome and ribosome recycling. Ribosome recycling follows the termination of protein synthesis and is aided by ribosome recycling factor (RRF) in bacteria. Aminoglycosides are widely used antibiotics that, among their effects, inhibit ribosome recycling. I will present x-ray crystal structures of the E. coli 70S ribosome with RRF and/or aminoglycosides bound that provide a structural explanation for aminoglycoside inhibition of ribosome recycling. I will also present structures of the E. coli 70S ribosome complexed with the antibiotic spectinomycin, which inhibits translocation. The structures with spectinomycin, together with biochemical experiments carried out in collaboration with Kurt Fredrick, provide an explanation for the specific step in translocation inhibited by spectinomycin.

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