Analysis of action of the wobble adenine on codon reading within the ribosome.
Computer graphics simulation of the interaction between the codon-anticodon duplexes containing adenine in the first (wobble) position of the anticodons, and bound to the ribosomal A- and P-sites, was made. This demonstrated that widespread use of adenine in the wobble position in anticodons should lead to a low efficiency of ribosomal translation, since the wobble A of the P-site tRNA weakens the codon-dependent binding of aminoacyl-tRNA at the A-site via interduplex interaction. Besides the canonical partner U, the wobble A of aminoacyl-tRNA can recognize A, C, G in the third position of the codon by the formation of the propeller twist in the wobble pairs AA, AC, AG. The conversion of the wobble A into inosine improves its pairing with the codon bases (the pairs IA and IC, unlike AA and AC, should not form the propeller twist leading to the deformation of base-base hydrogen bonds) and should reduce an adverse effect of the P-site wobble adenine on the formation of the A-site duplex. The consequence of the interaction between the ribosomal P- and E-site duplexes has been formulated. According to this the E-site wobble A should enhance the probability of frameshifting. These properties of the wobble A and I could be a reason why A is very rarely observed in the first anticodon position and why evolutionary processes have developed the enzyme which modifies the wobble A to I. The results obtained can be subjected to direct experimental tests.
Lim
V I
VI
Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region.
D000225:Adenine; D000926:Anticodon / Q000737:chemistry / Q000378:metabolism; D001482:Base Composition; D003062:Codon / Q000737:chemistry / Q000378:metabolism*; D003196:Computer Graphics; D003198:Computer Simulation; D006860:Hydrogen Bonding; D008957:Models, Genetic; D008958:Models, Molecular; D012345:RNA, Transfer, Amino Acid-Specific / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*
D000926:Anticodon; D003062:Codon; D012345:RNA, Transfer, Amino Acid-Specific; D000225:Adenine