Elongation arrest by SecM via a cascade of ribosomal RNA rearrangements.
In E. coli, the SecM nascent polypeptide causes elongation arrest, while interacting with 23S RNA bases A2058 and A749-753 in the exit tunnel of the large ribosomal subunit. We compared atomic models fitted by real-space refinement into cryo-electron microscopy reconstructions of a pretranslocational and SecM-stalled E. coli ribosome complex. A cascade of RNA rearrangements propagates from the exit tunnel throughout the large subunit, affecting intersubunit bridges and tRNA positions, which in turn reorient small subunit RNA elements. Elongation arrest could result from the inhibition of mRNA.(tRNAs) translocation, E site tRNA egress, and perhaps translation factor activation at the GTPase-associated center. Our study suggests that the specific secondary and tertiary arrangement of ribosomal RNA provides the basis for internal signal transduction within the ribosome. Thus, the ribosome may itself have the ability to regulate its progression through translation by modulating its structure and consequently its receptivity to activation by cofactors.
Mitra
Kakoli
K
Howard Hughes Medical Institute, Health Research, Inc., at the Wadsworth Center, Empire State Plaza, Albany, New York 12201, USA.
Schaffitzel
Christiane
C
Fabiola
Felcy
F
Chapman
Michael S
MS
Ban
Nenad
N
Frank
Joachim
J
D020285:Cryoelectron Microscopy; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D046911:Macromolecular Substances; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D010441:Peptide Chain Elongation, Translational; D011487:Protein Conformation; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012338:RNA, Ribosomal, 23S / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D029968:Escherichia coli Proteins; D046911:Macromolecular Substances; D012329:RNA, Bacterial; D012335:RNA, Ribosomal; D012338:RNA, Ribosomal, 23S; C497347:SecM protein, E coli; D014157:Transcription Factors