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Molecular dynamics simulations of human tRNA Lys,3 UUU: the role of modified bases in mRNA recognition.

McCrate NE, Varner ME, Kim KI, Nagan MC - Nucleic Acids Res. (2006)

Bottom Line: Guenther, A.The ms2t6 modification at position 37 is required for maintenance of this structure and reduces solvent accessibility of U36.A water molecule does coordinate to psi39 most of the simulation time but weakly, as most of the residence lifetimes are <40 ps.

View Article: PubMed Central - PubMed

Affiliation: Division of Science, Truman State University, 100 East Normal, Kirksville MO 63501, USA.

ABSTRACT
Accuracy in translation of the genetic code into proteins depends upon correct tRNA-mRNA recognition in the context of the ribosome. In human tRNA(Lys,3)UUU three modified bases are present in the anticodon stem-loop--2-methylthio-N6-threonylcarbamoyladenosine at position 37 (ms2t6A37), 5-methoxycarbonylmethyl-2-thiouridine at position 34 (mcm5s2U34) and pseudouridine (psi) at position 39--two of which, ms2t6A37 and mcm5s2U34, are required to achieve wild-type binding activity of wild-type human tRNA(Lys,3)UUU [C. Yarian, M. Marszalek, E. Sochacka, A. Malkiewicz, R. Guenther, A. Miskiewicz and P. F. Agris (2000) Biochemistry, 39, 13390-13395]. Molecular dynamics simulations of nine tRNA anticodon stem-loops with different combinations of nonstandard bases were performed. The wild-type simulation exhibited a canonical anticodon stair-stepped conformation. The ms2t6 modification at position 37 is required for maintenance of this structure and reduces solvent accessibility of U36. Ms2t6A37 generally hydrogen bonds across the loop and may prevent U36 from rotating into solution. A water molecule does coordinate to psi39 most of the simulation time but weakly, as most of the residence lifetimes are <40 ps.

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Stair-stepped conformation. (A) Stair-stepped conformation of the anticodon bases from the side (left) and from above (right) with dx, dy and dz parameters shown. (B) Snapshot of the wild-type simulation showing ms2t6A37 hydrogen bonding across the loop (left) and a snapshot of the ASLLys,3 ψ39 simulation when U36 is rotated into solution (right).
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fig3: Stair-stepped conformation. (A) Stair-stepped conformation of the anticodon bases from the side (left) and from above (right) with dx, dy and dz parameters shown. (B) Snapshot of the wild-type simulation showing ms2t6A37 hydrogen bonding across the loop (left) and a snapshot of the ASLLys,3 ψ39 simulation when U36 is rotated into solution (right).

Mentions: In the fully modified ASL structure including mcm5s2U34, ms2t6A37 and ψ39 (wild-type ASLLys,3), the structure retained a stair-stepped conformation, in which the uridines (Figure 3) are offset and nearly parallel to each other, observed previously in the X-ray crystal structures of free human tRNALys,3 (30) and when E.coli t6A ASLLys, pairs with its cognate mRNA codon in the context of the ribosome (19).


Molecular dynamics simulations of human tRNA Lys,3 UUU: the role of modified bases in mRNA recognition.

McCrate NE, Varner ME, Kim KI, Nagan MC - Nucleic Acids Res. (2006)

Stair-stepped conformation. (A) Stair-stepped conformation of the anticodon bases from the side (left) and from above (right) with dx, dy and dz parameters shown. (B) Snapshot of the wild-type simulation showing ms2t6A37 hydrogen bonding across the loop (left) and a snapshot of the ASLLys,3 ψ39 simulation when U36 is rotated into solution (right).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1636460&req=5

fig3: Stair-stepped conformation. (A) Stair-stepped conformation of the anticodon bases from the side (left) and from above (right) with dx, dy and dz parameters shown. (B) Snapshot of the wild-type simulation showing ms2t6A37 hydrogen bonding across the loop (left) and a snapshot of the ASLLys,3 ψ39 simulation when U36 is rotated into solution (right).
Mentions: In the fully modified ASL structure including mcm5s2U34, ms2t6A37 and ψ39 (wild-type ASLLys,3), the structure retained a stair-stepped conformation, in which the uridines (Figure 3) are offset and nearly parallel to each other, observed previously in the X-ray crystal structures of free human tRNALys,3 (30) and when E.coli t6A ASLLys, pairs with its cognate mRNA codon in the context of the ribosome (19).

Bottom Line: Guenther, A.The ms2t6 modification at position 37 is required for maintenance of this structure and reduces solvent accessibility of U36.A water molecule does coordinate to psi39 most of the simulation time but weakly, as most of the residence lifetimes are <40 ps.

View Article: PubMed Central - PubMed

Affiliation: Division of Science, Truman State University, 100 East Normal, Kirksville MO 63501, USA.

ABSTRACT
Accuracy in translation of the genetic code into proteins depends upon correct tRNA-mRNA recognition in the context of the ribosome. In human tRNA(Lys,3)UUU three modified bases are present in the anticodon stem-loop--2-methylthio-N6-threonylcarbamoyladenosine at position 37 (ms2t6A37), 5-methoxycarbonylmethyl-2-thiouridine at position 34 (mcm5s2U34) and pseudouridine (psi) at position 39--two of which, ms2t6A37 and mcm5s2U34, are required to achieve wild-type binding activity of wild-type human tRNA(Lys,3)UUU [C. Yarian, M. Marszalek, E. Sochacka, A. Malkiewicz, R. Guenther, A. Miskiewicz and P. F. Agris (2000) Biochemistry, 39, 13390-13395]. Molecular dynamics simulations of nine tRNA anticodon stem-loops with different combinations of nonstandard bases were performed. The wild-type simulation exhibited a canonical anticodon stair-stepped conformation. The ms2t6 modification at position 37 is required for maintenance of this structure and reduces solvent accessibility of U36. Ms2t6A37 generally hydrogen bonds across the loop and may prevent U36 from rotating into solution. A water molecule does coordinate to psi39 most of the simulation time but weakly, as most of the residence lifetimes are <40 ps.

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