Kinetic analysis of late steps of eukaryotic translation initiation

By M. Acker, B. Shin, J. Nanda, A. Saini, T. Dever, J. Lorsch. 2008

79 citations recorded by the source corpus.

Summary Little is known about the molecular mechanics of the late events of translation initiation in eukaryotes. We present a kinetic dissection of the transition from a pre-initiation complex (PIC) after start codon recognition to the final 80S initiation complex (IC). The resulting framework reveals that eIF5B actually accelerates the rate of ribosomal subunit joining and this acceleration is influenced by the conformation of the GTPase active site of the factor mediated by the bound nucleotide. eIF1A accelerates joining through its C-terminal interaction with eIF5B, and eIF1A release from the initiating ribosome, which occurs only after subunit joining, is accelerated by GTP hydrolysis by eIF5B. Following subunit joining, GTP hydrolysis by eIF5B alters the conformation of the final IC and clears a path to promote rapid release of eIF1A. Our data, coupled with previous work, indicate that eIF1A is present on the ribosome throughout the entire initiation process and plays key roles at every stage.

Subfields: Molecular Biology

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Citations in the corpus

A structural inventory of native ribosomal ABCE1‐43S pre‐initiation complexes (2020, unknown): “Subsequently, initiation factors apart from eIF1A and eIF3 dissociate (Mohammad et al , 2017; Sha et al , 2009) and subunit joining with the 60S LSU is then mediated by the GTPase eIF5B (Acker et al , 2006; Acker et al , 2009; Lee et al , 2002; Pestova et al , 2000).”
THE MECHANISM OF EUKARYOTIC TRANSLATION INITIATION AND PRINCIPLES OF ITS REGULATION (2010, background): “This indicates that eIF1A remains associated with ribosomal complexes throughout the subunit joining process and dissociates from assembled ribosomes with eIF5”
eIF5B employs a novel domain release mechanism to catalyze ribosomal subunit joining (2014, background): “Tel: +49 551 3914079; Fax: +49 551 3914082; E-mail: bkuhle@gwdg.de ª 2014 The Authors The EMBO Journal Vol 33 | No 10 | 2014 1177 GTP-dependent manner (Acker et al, 2009; Pestova et al, 2000).”
The scanning mechanism of eukaryotic translation initiation. (2014, background): “Ribosome-stimulated GTP hydrolysis by eIF5B is dispensable for subunit joining (233) but is needed for a functional 80S IC (240– 242) because GTP hydrolysis reduces eIF5B affinity for the 80S IC (233) and triggers its release (242).”
Molecular architecture of a eukaryotic translational initiation complex (2013, background): “However, it is known that eIF5B also accelerates the rate of 60S recruitment (26, 27).”