Paula M. Petrone, Christopher D. Snow, Del Lucent, and Vijay S. Pande
Proceedings of the National Academy of Sciences, USA 2008
SUMMARY The ribosome is a fascinating molecular machine, responsible for the synthesis of proteins. For this reason it is of fundamental importance to protein folding (as the last step in the central dogma of biology) as well as to human health (since the ribosome is the target of a very large fraction of antibiotics). One of the questions revolving around ribosome function is why is there a large tunnel inside the ribosome, through which proteins exit after being synthesized. In this paper, we used “bigWU” classic clients (clients which allow larger systems to run) since the ribosome is so huge that it would not run on regular classic clients. The primary goal of this paper was to analyze the surface of the ribosome tunnel. Understanding the nature of this surface would be useful for both understanding the fundamental nature of protein synthesis as well as how key antibiotics interact with the ribosome. An interesting related discovery was the identification of a potential “ribosome gate” which can open and close selectively, based on what is interacting with the gate. This suggests novel hypotheses for several aspects of ribosome function as well as interesting new directions for work on studying the ribosome and for new routes for antibiotics.
ABSTRACT The ribosome is a large complex catalyst responsible for the synthesis of new proteins, an essential function for life. New proteins emerge from the ribosome through an exit tunnel as nascent polypeptide chains. Recent findings indicate that tunnel interactions with the nascent polypeptide chain might be relevant for the regulation of translation. However, the specific ribosomal structural features that mediate this process are unknown. Performing molecular dynamics simulations, we are studying the interactions between components of the ribosome exit tunnel and different chemical probes (specifically different amino acid side chains or monovalent inorganic ions). Our free-energy maps describe the physicochemical environment of the tunnel, revealing binding crevices and free-energy barriers for single amino acids and ions. Our simulations indicate that transport out of the tunnel could be different for diverse amino acid species. In addition, our results predict a notable protein–RNA interaction between a flexible 23S rRNA tetraloop (gate) and ribosomal protein L39 (latch) that could potentially obstruct the tunnel’s exit. By relating our simulation data to earlier biochemical studies, we propose that ribosomal features at the exit of the tunnel can play a role in the regulation of nascent chain exit and ion flux. Moreover, our free-energy maps may provide a context for interpreting sequence-dependent nascent chain phenomenology.