Role of S-turn2 in the structure, dynamics, and function of mitochondrial ribosomal A-site. A bioinformatics and molecular dynamics simulation study.
The mRNA decoding site (A-site) in the small ribosomal subunit controls fidelity of the translation process. Here, using molecular dynamics simulations and bioinformatic analyses, we investigated the structural dynamics of the human mitochondrial A-site (native and A1490G mutant) and compared it with the dynamics of the bacterial A-site. We detected and characterized a specific RNA backbone configuration, S-turn2, which occurs in the human mitochondrial but not in the bacterial A-site. Mitochondrial and bacterial A-sites show different propensities to form S-turn2 that may be caused by different base-pairing patterns of the flanking nucleotides. Also, the S-turn2 structural stability observed in the simulations supports higher accuracy and lower speed of mRNA decoding in mitochondria in comparison with bacteria. In the mitochondrial A-site, we observed collective movement of stacked nucleotides A1408·C1409·C1410, which may explain the known differences in aminoglycoside antibiotic binding affinities toward the studied A-site variants.
Department of Biophysics, Institute of Experimental Physics and ∥Centre of New Technologies, University of Warsaw , Żwirki i Wigury 93, 02-089 Warsaw, Poland.
Joanna
J
Panecka
Marek
M
Havrila
Kamila
K
Réblová
Jiří
J
Šponer
Joanna
J
Trylska
D001419:Bacteria / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020029:Base Pairing; D001665:Binding Sites; D019295:Computational Biology; D006801:Humans; D006860:Hydrogen Bonding; D008928:Mitochondria / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D012333:RNA, Messenger