Viewing the mechanisms of translation through the computational microscope

James Gumbart, Eduard Schreiner, Leonardo G. Trabuco, Kwok Yan Chan, Klaus J Schulten

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Introduction. Biological molecular machines span a range of sizes, from the 80-Å-sized helicases (e.g., PcrA) (Dittrich and Schulten, 2006; Dittrich et al., 2006), to the 250-Å-sized ATP synthase (Aksimentiev et al., 2004), to the 10-μm-long Bacterial flagellum (Arkhipov et al., 2006; Kitao et al., 2006). The machines all share certain traits, particularly the ability to utilize energy to perform useful work. Like macroscopic machines, those on the molecular scale are typically comprised of different components that carry out a cycle of well-regulated steps. Unlike macroscopic machines, however, molecular machines must contend with, and even take advantage of, thermal fluctuations that are omnipresent at their scale. A quintessential example of a large molecular machine, the ribosome, is found in all organisms and in all cells. It is a large (2.5–4.5 MDa) nucleo-protein complex responsible for translating a cell’s genetic information into proteins (Korostelev et al., 2008; Steitz, 2008; Schmeing and Ramakrishnan, 2009; Frank and Gonzalez, Jr., 2010). The ribosome is composed of a multitude of interacting components (more than fifty) that assemble into two subunits, denoted large and small. Translation can be broken down into four fundamental stages, initiation, elongation, termination and recycling, each composed of multiple steps and requiring the involvement of additional specialized components. In the first stage (step 1), the two ribosomal subunits join together with a messenger RNA (mRNA) strand to initiate its translation. Initiation is followed by elongation (step 2) of the nascent protein, enabled via the delivery of each amino acid by a transfer RNA (tRNA) in complex with elongation factor Tu (EF-Tu) (Agirrezabala and Frank, 2009). The translocation of tRNAs through the ribosome also occurs in discrete steps, brought about by a large-scale ratchet-like motion of the two ribosomal subunits (Frank and Agrawal, 2000; Dunke and Cate, 2010). The nascent protein leaves the ribosome through an exit tunnel, which is not merely a passive conduit but can play a regulatory role. Some nascent proteins control their own translation through specific protein-tunnel interactions that halt translation or recruit other factors to the ribosome. For example, proteins not destined for immediate extrusion into the cytoplasm can direct the ribosome to a protein-conducting translocon, the SecY/Sec61 complex, which then aids the proper localization of the nascent protein (Rapoport, 2007). After elongation is completed, translation is terminated (step 3) and the ribosomal components are all recycled (step 4), making them available for the next mRNA.

Original languageEnglish (US)
Title of host publicationMolecular Machines in Biology
Subtitle of host publicationWorkshop of the Cell
PublisherCambridge University Press
Pages142-157
Number of pages16
ISBN (Electronic)9781139003704
ISBN (Print)9780521194280
DOIs
StatePublished - Jan 1 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Gumbart, J., Schreiner, E., Trabuco, L. G., Chan, K. Y., & Schulten, K. J. (2011). Viewing the mechanisms of translation through the computational microscope. In Molecular Machines in Biology: Workshop of the Cell (pp. 142-157). Cambridge University Press. https://doi.org/10.1017/CBO9781139003704.010