A Model for Nonstoichiometric, Cotranslational Protein Scission in Eukaryotic Ribosomes
✍ Scribed by Martin D. Ryan; Michelle Donnelly; Arwel Lewis; Amit P. Mehrotra; John Wilkie; David Gani
- Publisher
- Elsevier Science
- Year
- 1999
- Tongue
- English
- Weight
- 915 KB
- Volume
- 27
- Category
- Article
- ISSN
- 0045-2068
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✦ Synopsis
The aphthovirus 2A region apparently responsible for the hydrolytic cleavage of a single large polyprotein at a Gly-Pro linkage is only 18 amino acid residues long and is evidently not a proteinase. Here we describe the construction of reporter recombinant polyproteins and provide the results of further mutagenesis experiments designed to test the functions of specific amino acid residues within the foot-and-mouth disease virus (FMDV) 2A region. These results show that a Gly-Pro amide bond is not actually synthesized. The result can be rationalized into a kinetic and structural model for cotranslational aphtho-and cardiovirus polyprotein cleavage in which hydrolysis is mediated by a ribosomally bound 2A polypeptidyl-tRNA molecule at its own 3Ј-O acyl adenosyl ester linkage. The possible role of the 3-D structure of the 2A polypeptide in preventing peptide bond formation but in allowing the synthesis of the downstream polypeptide sequence is discussed within the context of the new findings.