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.
