Disease relevance of MES1

• We have analysed by site-directed mutagenesis the peptide region 655 to 663 of the yeast MetRS that is equivalent to the anticodon binding region of the E. coli methionine enzyme [1].

High impact information on MES1

• Arc1p is linked to MetRS and GluRS through its amino-terminal domain, while its middle and carboxy-terminal parts comprise a novel tRNA-binding domain [2].
• However, when their assembly into a complex is inhibited, significant amounts of MetRS, GluRS and Arc1p can enter the nucleus [3].
• Thus, Cca1p and Mes1p seem to function in a Los1p-independent tRNA nuclear export pathway [4].
• The mutation was cloned on a multicopy plasmid by gap repair of a plasmid bearing the wild type MES1 gene for a fragment corresponding to the mes 1 mutation [5].
• The major MES1 transcript is not affected by the general control or starvation for several different amino acids, including methionine [6].

Chemical compound and disease context of MES1

• As for Escherichia coli methionine tRNAs, the anticodon triplet of yeast tRNA(Met) plays an important role in the recognition by the yeast methionyl-tRNA synthetase (MetRS), indicating that this determinant for methionine identity is conserved in yeast [1].

Biological context of MES1

• Analysis of an 11.6 kb region from the right arm of chromosome VII of Saccharomyces cerevisiae between the RAD2 and the MES1 genes reveals the presence of three new genes [7].
• Sequence analysis of an 11,628 bp DNA segment from the right arm of Saccharomyces cerevisiae chromosome VII revealed the presence of the 5' end of the RAD2 gene, the MES1 gene and six open reading frames (ORFs) each longer than 300 bp [7].
• In plant MetRS, the EMAPII-like domain is fused to the catalytic core of the synthetase and acts as a cis-acting tIF for aminoacylation [8].
• Similarly, it is the N-terminal domain of Arc1p that contains distinct but overlapping binding sites for MetRS and GluRS [3].
• The k(cat) defect of the tRNA(Met) mutant may arise from a failure to overcome an increase of the free energetic cost of distorting the more stable tRNA structure and/or a tRNA based MetRS conformational change required for formation of transition state of aminoacylation [9].

Physical interactions of MES1

• Complementation of yeast Arc1p by the p43 component of the human multisynthetase complex does not require its association with yeast MetRS and GluRS [8].

Other interactions of MES1

• Arc1p is associated with two proteins which were identified as methionyl-tRNA and glutamyl-tRNA synthetase (MetRS and GluRS) by a new mass spectrometry method [10].

Analytical, diagnostic and therapeutic context of MES1

• Dissection of the yeast cytoplasmic initiator tRNA(Met) into two helical domains, the T psi C acceptor and anticodon minihelices, failed to show anminoacylation and binding of the acceptor minihelix by the yeast methionyl-tRNA synthetase (MetRS) even in the presence of the anticodon minihelix [11].
• Using serum albumin as an inhibitor of adhesion of L5 to the microconcentrators which was used to concentrate the final product, a distinct L5 band was detected on SDS-PAGE, the intensity of which was comparable to that of the MetRS band [12].
• The dissociated MetRS complex fraction was purified by gel filtration followed by tRNA-Sepharose chromatography using partially purified tRNA(met) in Method I, and by hydrophobic interaction chromatography in Method II [12].

References