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The bacterial and mitochondrial ribosomal A-site molecular switches possess different conformational substates.

Kondo J, Westhof E - Nucleic Acids Res. (2008)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Architecture et Réactivité de l'ARN, Université Louis Pasteur, Institut de Biologie Moléculaire et Cellulaire, CNRS, 15 rue René Descartes, 67084 Strasbourg, France.

ABSTRACT
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.

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Secondary structures of the bacterial, H. sapiens mitochondrial wild-type and its A1555G mutant A sites. The nucleotides different from those in the bacterial A site are colored in red. The G1555 residue in the A1555G mutant is colored in blue.
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Figure 1: Secondary structures of the bacterial, H. sapiens mitochondrial wild-type and its A1555G mutant A sites. The nucleotides different from those in the bacterial A site are colored in red. The G1555 residue in the A1555G mutant is colored in blue.

Mentions: The secondary structure of the H. sapiens mitochondrial A site is very similar to that of the bacterial A site (Figure 1) (12). Differences are found at residue 1556 (1491 in bacterial numbering), which is a C in mitochondria and a G in bacteria, and at the base pair between 1494 and 1555 (1410 and 1490 in bacterial numbering), which is a CoA opposition in mitochondria and an A-U (66.5%) or a G=C (26.4%) base pair in bacteria (13). It is important to note that residue 1492 (1408 in bacterial numbering) is an A in the H. sapiens mitochondrial as in bacterial A sites, while it is a G in the H. sapiens cytoplasmic A site (11,12). Because of the similarity in the secondary structure of the A site, it has long been believed that the H. sapiens mitochondrial A site has functional characteristics and tertiary structure similar to those of the bacterial A site.Figure 1.


The bacterial and mitochondrial ribosomal A-site molecular switches possess different conformational substates.

Kondo J, Westhof E - Nucleic Acids Res. (2008)

Secondary structures of the bacterial, H. sapiens mitochondrial wild-type and its A1555G mutant A sites. The nucleotides different from those in the bacterial A site are colored in red. The G1555 residue in the A1555G mutant is colored in blue.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2377432&req=5

Figure 1: Secondary structures of the bacterial, H. sapiens mitochondrial wild-type and its A1555G mutant A sites. The nucleotides different from those in the bacterial A site are colored in red. The G1555 residue in the A1555G mutant is colored in blue.
Mentions: The secondary structure of the H. sapiens mitochondrial A site is very similar to that of the bacterial A site (Figure 1) (12). Differences are found at residue 1556 (1491 in bacterial numbering), which is a C in mitochondria and a G in bacteria, and at the base pair between 1494 and 1555 (1410 and 1490 in bacterial numbering), which is a CoA opposition in mitochondria and an A-U (66.5%) or a G=C (26.4%) base pair in bacteria (13). It is important to note that residue 1492 (1408 in bacterial numbering) is an A in the H. sapiens mitochondrial as in bacterial A sites, while it is a G in the H. sapiens cytoplasmic A site (11,12). Because of the similarity in the secondary structure of the A site, it has long been believed that the H. sapiens mitochondrial A site has functional characteristics and tertiary structure similar to those of the bacterial A site.Figure 1.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Architecture et Réactivité de l'ARN, Université Louis Pasteur, Institut de Biologie Moléculaire et Cellulaire, CNRS, 15 rue René Descartes, 67084 Strasbourg, France.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus