Limits...
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.

Show MeSH

Related in: MedlinePlus

The A1555G mutant of the H. sapiens mitochondrial A site in the first ‘off’ state. (a) Secondary structure and stereoview. (b–h) Atomic details of each base pair of the A site. Three universally conserved adenine residues, A1492, A1557 and A1558 (A1408, A1492 and A1493 in bacterial numbering), are colored in orange, blue and red, respectively. Two nucleotides different from those in the bacterial A site, G1555 and C1556 (G1490 and C1491 in bacterial numbering), are colored in cyan and green, respectively. The hydrogen bonds are represented by black dashed lines.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2377432&req=5

Figure 5: The A1555G mutant of the H. sapiens mitochondrial A site in the first ‘off’ state. (a) Secondary structure and stereoview. (b–h) Atomic details of each base pair of the A site. Three universally conserved adenine residues, A1492, A1557 and A1558 (A1408, A1492 and A1493 in bacterial numbering), are colored in orange, blue and red, respectively. Two nucleotides different from those in the bacterial A site, G1555 and C1556 (G1490 and C1491 in bacterial numbering), are colored in cyan and green, respectively. The hydrogen bonds are represented by black dashed lines.

Mentions: A stereoview with the secondary structure of the A1555G mutant of the H. sapiens mitochondrial A site in the first ‘off’ state is shown in Figure 5a. Its overall conformation is very similar to that of the ‘off’ state of the mitochondrial wild-type A site mentioned above (RMSD = 1.0Å) (Figure 2a). Only one difference between them is found at the bottom of the A-site internal loop. As expected, a Watson-Crick G1555=C1494 base pair is observed in the A1555G mutant (Figure 5h) instead of the A1555oC1494 base pair in the wild-type (Figure 4h). As observed in the wild-type ‘off’ state, there are three stacking columns; one contains all residues on the long strand except A1558, and others are C1488-G1489-U1490-C1491 and A1492-C1493-C1494 on the short strand (Supplementary Figure 10c).Figure 5.


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

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

The A1555G mutant of the H. sapiens mitochondrial A site in the first ‘off’ state. (a) Secondary structure and stereoview. (b–h) Atomic details of each base pair of the A site. Three universally conserved adenine residues, A1492, A1557 and A1558 (A1408, A1492 and A1493 in bacterial numbering), are colored in orange, blue and red, respectively. Two nucleotides different from those in the bacterial A site, G1555 and C1556 (G1490 and C1491 in bacterial numbering), are colored in cyan and green, respectively. The hydrogen bonds are represented by black dashed lines.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 5: The A1555G mutant of the H. sapiens mitochondrial A site in the first ‘off’ state. (a) Secondary structure and stereoview. (b–h) Atomic details of each base pair of the A site. Three universally conserved adenine residues, A1492, A1557 and A1558 (A1408, A1492 and A1493 in bacterial numbering), are colored in orange, blue and red, respectively. Two nucleotides different from those in the bacterial A site, G1555 and C1556 (G1490 and C1491 in bacterial numbering), are colored in cyan and green, respectively. The hydrogen bonds are represented by black dashed lines.
Mentions: A stereoview with the secondary structure of the A1555G mutant of the H. sapiens mitochondrial A site in the first ‘off’ state is shown in Figure 5a. Its overall conformation is very similar to that of the ‘off’ state of the mitochondrial wild-type A site mentioned above (RMSD = 1.0Å) (Figure 2a). Only one difference between them is found at the bottom of the A-site internal loop. As expected, a Watson-Crick G1555=C1494 base pair is observed in the A1555G mutant (Figure 5h) instead of the A1555oC1494 base pair in the wild-type (Figure 4h). As observed in the wild-type ‘off’ state, there are three stacking columns; one contains all residues on the long strand except A1558, and others are C1488-G1489-U1490-C1491 and A1492-C1493-C1494 on the short strand (Supplementary Figure 10c).Figure 5.

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