Disease relevance of ARC1

• We report identification of seven proteins from Escherichia coli (AroF, DnaK, MutM, PolA, TnaA, TufA, and UvrA) and two proteins from bakers' yeast (ARC1 and Ygl245wp) reactive for AP sites in this system [1].

High impact information on ARC1

• We show here that association of Arc1p with MetRS and GluRS is required in vivo for effective recruitment of the corresponding cognate tRNAs within this complex [2].
• Similarly, it is the N-terminal domain of Arc1p that contains distinct but overlapping binding sites for MetRS and GluRS [3].
• Arc1p was found in a screen for components that interact genetically with Los1p, a nuclear pore-associated yeast protein involved in tRNA biogenesis [4].
• Furthermore, Arc1p, which is allelic to the quadruplex nucleic acid binding protein G4p1, exhibits specific binding to tRNA as determined by gel retardation and UV-cross-linking [4].
• In contrast to the known carboxylases, however, in vitro biotinylation of Arc1p is incomplete and increases with BPL1 overexpression [5].

Biological context of ARC1

• These results show that p43 and Arc1p are able to facilitate tRNA aminoacylation in vivo even if they do not interact physically with the synthetases [6].
• Because Arc1p also interacts with yeast GluRS, restoration of cell growth could be due at least in part to its role of cofactor for that enzyme [6].
• Thus, the cytoplasmic location of Arc1p is maintained by Xpo1p-dependent nuclear export and Arc1p could act as an adapter in the nucleocytoplasmic trafficking of tRNA and/or the tRNA-aminoacylation machinery [7].
• Identification of the tRNA-binding protein Arc1p as a novel target of in vivo biotinylation in Saccharomyces cerevisiae [5].
• In accordance to this fact, Arc1p lacks the canonical consensus sequence of known biotin binding domains, and the bacterial biotin:protein ligase, BirA, is unable to use Arc1p as a substrate [5].

Anatomical context of ARC1

• Los1p facilitates tRNA translocation across the nuclear pore complex whereas Arc1p plays a role in delivering some species of tRNA exiting the nucleus to their cognate aminoacyl-tRNA synthetases [8].

Associations of ARC1 with chemical compounds

• Using 14C-labeled biotin, the cofactor was shown to be incorporated into Arc1p by covalent and alkali-stable linkage [5].
• Mutational studies revealed that biotinylation occurs at lysine 86 within the N-terminal domain of Arc1p [5].
• Remarkably, not only biotinylated but also the biotin-free Arc1p obtained by replacement of lysine 86 with arginine were capable of restoring Arc1p function in both arc1Delta and arc1Deltalos1Delta mutants, indicating that biotinylation of Arc1p is not essential for activity [5].
• The structure of the interacting domain of its accessory protein Arc1p was determined and refined to 1.9 A resolution in a crystal form containing 20 monomers organized in five tetramers per asymmetric unit (space group C2, unit-cell parameters a = 222, b = 89, c = 127 A, beta = 99.4 degrees ) [9].
• The genes encoding the transcription factor yTAFII60, the G4p1 protein and a putative glucose transporter are contained in a 12.3 kb DNA fragment on the left arm of Saccharomyces cerevisiae chromosome VII [10].

Physical interactions of ARC1

• In this work, in order to localize free Arc1 we abolished complex assembly by deleting the appended domains from both MetRS and GluRS [7].

Other interactions of ARC1

• 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 [4].
• However, NLS-Arc1p accumulated in the nucleus when Xpo1/Crm1, the export receptor for NES-containing cargo proteins, was mutated [7].
• Nuclear export of tRNA in Saccharomyces cerevisiae involves Los1p and Arc1p [8].

Analytical, diagnostic and therapeutic context of ARC1

• Expression, purification, crystallization and preliminary phasing of the heteromerization domain of the tRNA-export and aminoacylation cofactor Arc1p from yeast [11].

References