Darrell R. Davis Department of Medicinal Chemistry Translation and tRNAs.

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Presentation transcript:

Darrell R. Davis Department of Medicinal Chemistry Translation and tRNAs

Ribosome

Overall Structure of Ribosome

RNA structures of Large Subunit

tRNAs on the Ribosome

Some Tetraloops in 16S RNA RNA Secondary Structure

tRNA Phe

Yeast tRNA Folding Saenger

Unusual Pairing in tRNAs

Base Stacking and Intercalation

U-turns, The Anticodon

Circles represent nucleosides that are Always present. Gold are invariant or semivariant The RNA Modification Database tRNA Modifications in Eukarya and Bacteria

Grosjean, H., Chantrenne, H. (1980) Mol. Biol. Biochem. Biophys.32, RNA (0.1 mM, 1 M NaCl)  G° 37 kcal/mol  H° kcal/mol T m °C GGGCCC CCCGGG AAAUUU UUUAAA AAA UUU Intrinsic properties of 3 base-pair RNA hairpin interactions

Human tRNA Lys,3 and E.coli tRNA Lys

Saenger (1988) “Principles of Nucleic Acid Structure” pp. 347 ms 2 t 6 A (A9) Adenosine Uridine Pseudouridine (  )(F) mcm 5 s 2 U (U9)mnm 5 s 2 U (U8) Codon-Anticodon Interactions

Effects of mnm 5 s 2 U on base-pairing and stacking - s 2 U base pair stabilization

Summary The ribosome is a large “molecular machine” for making proteins tRNAs bind 3 sites on the ribosome, Amino-acyl, Peptidyl, Exit RNAs (rRNA, tRNA, and mRNA) are seldom “linear”, but fold into complex structures. tRNAs can all be folded into a “cloverleaf” secondary structure tRNAs all form an “L-shaped” 3D structure tRNAs contain many non-canonical pairs and triples Modifications are clustered in the functionally important areas Modifications are conserved in the 3 kingdoms of life. Modification in the tRNA anticodon help normalize the binding affinity for the mRNA.