Abstract:
:Although the structural core of the ribosome is conserved in all kingdoms of life, eukaryotic ribosomes are significantly larger and more complex than their bacterial counterparts. The extent to which these differences influence the molecular mechanism of translation remains elusive. Multiparticle cryo-electron microscopy and single-molecule FRET investigations of the mammalian pretranslocation complex reveal spontaneous, large-scale conformational changes, including an intersubunit rotation of the ribosomal subunits. Through structurally related processes, tRNA substrates oscillate between classical and at least two distinct hybrid configurations facilitated by localized changes in their L-shaped fold. Hybrid states are favored within the mammalian complex. However, classical tRNA positions can be restored by tRNA binding to the E site or by the eukaryotic-specific antibiotic and translocation inhibitor cycloheximide. These findings reveal critical distinctions in the structural and energetic features of bacterial and mammalian ribosomes, providing a mechanistic basis for divergent translation regulation strategies and species-specific antibiotic action.
journal_name
Mol Celljournal_title
Molecular cellauthors
Budkevich T,Giesebrecht J,Altman RB,Munro JB,Mielke T,Nierhaus KH,Blanchard SC,Spahn CMdoi
10.1016/j.molcel.2011.07.040subject
Has Abstractpub_date
2011-10-21 00:00:00pages
214-24issue
2eissn
1097-2765issn
1097-4164pii
S1097-2765(11)00757-Xjournal_volume
44pub_type
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