Wobble base pairing

Watson-Crick wobble base pair mismatch mismatch mismatch... 

Figure 3 Cognate and near-cognate codon-anticodon interactions. The anticodon ioop of tRNA is shown as an example interacting with various codons on the mRNA. In correct, cognate codon-anticodon pairings, two Watson-Crick base pairs can be formed in the first two positions while the third position contains either a Watson-Crick or a wobble base pair.

I I I I I Watson-Crick pairs G-U wobble base pair /WWW exon... 

Murphy, F. V., 4th Ramakrishnan, V. Structure of a purine-purine wobble base pair in the decoding center of the ribosome. Nat. Struct. Mol. Biol. 2004,11, 1251-1252. 

Wobble Base pairing rules used for position... 

Figure 12-1. Codon-anticodon base pairing. Special wobble base-pairing rules apply to the third (3 ) position of the codon. The first (S ) position of the tRNA anticodon is frequently inosine (I) to provide this flexibility in hydrogen bonding.

Codons that specify the same amino acid are called synonyms. Most synonyms differ only in the third base of the codon for example GUU, GUC, GUA and GUG all code for valine. During protein synthesis, each codon is recognized by a triplet of bases, called an anticodon, in a specific tRNA molecule (see Topics G10 and H2). Each base in the codon base pairs with its complementary base in the anticodon. However, the pairing of the third base of a codon is less stringent than for the first two bases (i.e. there is some wobble base-pairing ) so that in some cases a single tRNA may base-pair with more than one codon. For example, phenylalanine tRNA, which has the anticodon GAA, recognizes both of the codons UUU and UUC. The third position of the codon is therefore also called the wobble position. 

Configuration XU22 (comparable to GU22, Fig. 16.14) is a wobble base pair and of importance for some transfer RNA s with hypoxanthine in the anticodon sequence (see Chap. 20). 

In nature, base pairs of the Watson-Crick type prevail [674] as described in the previous sections. However, there are some well-documented structures where other base pairs occur. In one type, illustrated in Fig. 20.4, the bases are in the canonical keto/amino forms but base pairs are in mismatch configurations called wobble base pairs [675]. They occur even systematically in interactions between messenger RNA (mRNA) and transfer RNA (tRNA), and appear to play a role in mutation processes during DNA replication. Another type of non-Watson-Crick base pairs is found if the bases occur in rare enol/imino forms. These are also believed to be involved in mutation processes, albeit by a mechanism other than wobble base pairs, vide infra. 

Systematic wobble base pairing was predicted on the basis of the genetic code. 

Fig. 20.4. Comparison of Watson-Crick (top) and wobble base pairs. Deviations from standard geometry are indicated by arrows. Atom designation o, oxygen small filled circle, hydrogen large filled circle, nitrogen thick line, glycosidic Cl -N bond...

During translation, the anticodon (on tRNA) and the codon (on mRNA) are arranged in the form of a short antiparallel double helix of the Watson-Crick type so that the base in 3 -position of the codon forms a base pair with the base in S -position of the anticodon. Because the number of tRNA s (and the number of anticodons) is limited, the same tRNA anticodon has to base-pair with several of the possible mRNA codons which differ in their 3 -position. Nature solves this problem by allowing nonstandard (wobble) base pairs ... 

The wobble base pairs are displayed in Fig. 20.4. In comparison with Watson-Crick base pairs, the positions of the glycosyl links differ, but their directions are more or less retained so that the short codon-anticodon double helix is smooth. Pyrimidine-pyrimidine base pairs U - U and U - C, which could also form (Part II, Chap. 16) are considered to be unlikely since their C(l,) -C(r) distances are about 2 A shorter than the 10.5 A in a Watson-Crick base pair. The long A-1 base pair with C(l ) -C(r) distance of about 13.5 A, as actually observed in a comparable crystalline base-pairing complex [678], is too long to be accommodated in a smooth double helix. It has been suggested therefore that inosine in syn form could mimic the Watson-Crick geometry [679]. 

Fig. 20.5 a, b. Schematic representation of hydration of a G-T wobble base pair in the Z-DNA type crystal structure of d(CGCGTG). Hydrogen-bonding distances to water molecules (W) and C(l )- -C(l ) distances given in A units. Left hydration is only by water molecules right hydration involves a cluster [Mg(H20)6]2+ [683]... 

Sato K, Tawarada R, Seio K, Sekine M. Synthesis and structural properties of new oUgodeoxynucleotide analogues containing a 2, 5 -internucleotidic squaryldiamide linkage capable of formation of a Watson-Crick base pair with adenine and a wobble base pair with guanine at the 3 -downstream junction site. Eur. J. Org. Chem. 2004 2142-2150. 

Figure 4 (sl, b) Hoogsteen and (c-e) wobble base-pairing schemes. I =inosine... 

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