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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.

Show MeSH
Secondary structure of human tRNALys,3 ASL. Chemical structures of modified bases found in ASLLys,3.
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fig1: Secondary structure of human tRNALys,3 ASL. Chemical structures of modified bases found in ASLLys,3.

Mentions: Functional groups in modified nucleosides can dramatically affect the ability of tRNA anticodons to recognize their cognate mRNA codon and therefore participate in accurate translation of the genetic code (15,16). The third human tRNA coding for lysine (tRNALys,3) contains three posttranscriptionally modified bases in the anticodon stem–loop (ASL, Figure 1). Biochemical assays have established that 5-methoxycarbonylmethyl-2-thiouridine at position 34 (mcm3s2U34) and 2-methylthio-N6-threonylcarbamoyl-adenosine at position 37 (ms2t6A37) are required to mimic wild-type human tRNALys,3 binding to programmed ribosomes (9). Pseudouridine (ψ) presence at position 39 is not critical to anticodon–codon recognition but has been shown to contribute to helical stability (17). Escherichia coli tRNALys,, analogous to its human counterpart, contains a 5-methylaminomethyluridine-2-thiouridine at position 34 (mnm5s2U34) and N6-threonylcarbamoyl-adenosine at position 37 (t6A37) that are both important for ribosomal A site binding (8,9,23), translocation from the A site (11) and discrimination between AAA and AAG codons (24,25).


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)

Secondary structure of human tRNALys,3 ASL. Chemical structures of modified bases found in ASLLys,3.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Secondary structure of human tRNALys,3 ASL. Chemical structures of modified bases found in ASLLys,3.
Mentions: Functional groups in modified nucleosides can dramatically affect the ability of tRNA anticodons to recognize their cognate mRNA codon and therefore participate in accurate translation of the genetic code (15,16). The third human tRNA coding for lysine (tRNALys,3) contains three posttranscriptionally modified bases in the anticodon stem–loop (ASL, Figure 1). Biochemical assays have established that 5-methoxycarbonylmethyl-2-thiouridine at position 34 (mcm3s2U34) and 2-methylthio-N6-threonylcarbamoyl-adenosine at position 37 (ms2t6A37) are required to mimic wild-type human tRNALys,3 binding to programmed ribosomes (9). Pseudouridine (ψ) presence at position 39 is not critical to anticodon–codon recognition but has been shown to contribute to helical stability (17). Escherichia coli tRNALys,, analogous to its human counterpart, contains a 5-methylaminomethyluridine-2-thiouridine at position 34 (mnm5s2U34) and N6-threonylcarbamoyl-adenosine at position 37 (t6A37) that are both important for ribosomal A site binding (8,9,23), translocation from the A site (11) and discrimination between AAA and AAG codons (24,25).

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.

Show MeSH