Thomas A. Steitz

Toward an Understanding of the Structural Basis of Crick’s Central Dogma


Abstract

For the past four decades, we have been pursuing a complete structural understanding of how DNA is replicated into DNA, how DNA is transcribed into RNA and how RNA is translated into protein. Understanding each of these steps in these complex processes requires the atomic structures of the complexes of the proteins/nucleic acids and substrates captured at each step in the process.

In my presentation, I shall concentrate primarily on a few recent studies: the cryostructure of the catabolite gene activator protein (CAP) in complex with RNA polymerase, the DNA substrate initiation site and a short RNA transcript. This is a research problem that we have been pursuing for decades until the recent cryo-EM revolution made it possible to solve its structure. I shall then turn to describing various structures of the ribosome in complex with mRNA, tRNAs and protein factors that enable and/or regulate the process of protein synthesis. We have also obtained the structures of the ribosome complexes with various small molecules, some of which are active antibiotics.


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