期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2008
卷号：105
期号：43
页码：16549-16554
DOI：10.1073/pnas.0801795105
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
