TCBG Seminar

Simulating the Conformational Changes of the Ribosome Observed in Cryo-EM Data

Dr. Kevin Y. Sanbonmatsu
Los Alamos National Laboratory
Los Alamos, NM

Monday, March 13, 2006
3:00 pm (CT)
3269 Beckman Institute


Decoding is the key step during protein synthesis that enables information transfer from RNA to protein, a process critical for the survival of all organisms. We have used large- scale all-atom simulations of the ribosome to understand a critical step of decoding. While the decoding problem has been studied for over four decades, the rate-limiting step of cognate tRNA selection has only recently been identified. This step, known as accommodation, involves the movement inside the ribosome of the aminoacyl-tRNA from the partially bound ‘A/T’ state to the fully bound ‘A/A’ state. Here, we show that a corridor of twenty universally conserved ribosomal RNA bases interact with the tRNA during the accommodation movement. Surprisingly, the tRNA is impeded by the A-loop (23S helix 92), instead of enjoying a smooth transition to the A/A state. In particular, universally conserved 23S ribosomal RNA bases U2492, C2556 and C2573 act as a three-dimensional gate, causing the acceptor stem to pause before allowing entrance into the peptidyl transferase center.

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