The bacterial and mitochondrial ribosomal A-site molecular switches possess different conformational substates.
The A site of the small ribosomal subunit participates in the fidelity of decoding by switching between two states, a resting 'off' state and an active decoding 'on' state. Eight crystal structures of RNA duplexes containing two minimal decoding A sites of the Homo sapiens mitochondrial wild-type, the A1555G mutant or bacteria have been solved. The resting 'off' state of the mitochondrial wild-type A site is surprisingly different from that of the bacterial A site. The mitochondrial A1555G mutant has two types of the 'off' states; one is similar to the mitochondrial wild-type 'off' state and the other is similar to the bacterial 'off' state. Our present results indicate that the dynamics of the A site in bacteria and mitochondria are different, a property probably related to the small number of tRNAs used for decoding in mitochondria. Based on these structures, we propose a hypothesis for the molecular mechanism of non-syndromic hearing loss due to the mitochondrial A1555G mutation.
Kondo
Jiro
J
Architecture et Réactivité de l'ARN, Université Louis Pasteur, Institut de Biologie Moléculaire et Cellulaire, CNRS, 15 rue René Descartes, 67084 Strasbourg, France.
Westhof
Eric
E
D018360:Crystallography, X-Ray; D034381:Hearing Loss / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D017354:Point Mutation; D012313:RNA / Q000737:chemistry* / Q000235:genetics; D012329:RNA, Bacterial / Q000737:chemistry*; D012333:RNA, Messenger / Q000737:chemistry; D000077278:RNA, Mitochondrial; D012335:RNA, Ribosomal / Q000737:chemistry*; D012343:RNA, Transfer / Q000737:chemistry
D012329:RNA, Bacterial; D012333:RNA, Messenger; D000077278:RNA, Mitochondrial; D012335:RNA, Ribosomal; D012313:RNA; D012343:RNA, Transfer