QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online July 30, 2004
doi: 10.1242/10.1242/jcs.01342

This Article Summary Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, S. W. Articles by Kim, S. Search for Related Content PubMed PubMed Citation Articles by Lee, S. W. Articles by Kim, S.

Aminoacyl-tRNA synthetase complexes: beyond translation

National Creative Research Initiatives Center for ARS Network, College of Pharmacy, Seoul National University, Seoul 151-742, Korea

View larger version (42K): [in a new window]   Fig. 1. Three-dimensional structure of the human multi-synthetase complex. (A) `Front' view. (B) `Side' view created by –90° rotation about the vertical axis. (C) `Top' view created by –90° rotation about the horizontal axis. The multi-synthetase complex was isolated from cultured human cells and prepared for electron microscopy by negatively staining with NanoVan (Wolfe et al., 2003). The volume was calculated from 8437 images, filtered to its resolution limit of 33 Å and presented at a threshold corresponding to a particle mass of 1.2x106 Da.

View larger version (28K): [in a new window]   Fig. 2. Functional domains in ARSs and ARS-related factors. The domains homologous to glutathione S-transferase (GST; red boxes) are shown in the N-terminal regions of MRS, EPRS and VRS, as well as in the C-terminal regions of p18 and p38. p38 also contains a leucine zipper motif (violet box) and is involved in macromolecular assembly of ARSs (Quevillon et al., 1999; Ahn et al., 2003). The sequence similarity between the helical tRNA-binding domain (green boxes) of MRS, GRS, HRS, WRS and the three repeated domains of EPRS was revealed by sequence alignment (Kaminska et al., 2001). Interestingly, these motifs are also involved in protein-protein interactions (Rho et al., 1996; Rho et al., 1998). DRS and KRS also contain helical tRNA-binding domains (TRBD; blue boxes), although they are not related to the motif mentioned above (Frugier et al., 2000; Francin et al., 2002). By contrast, the oligonucleotide-binding (OB) fold domains (blue boxes) in p43 and YRS are related (Renault et al., 2001). The similar RNA-binding OB folds can also be detected in some ARSs (human DRS, KRS and NRS; Escherichia coli MRS and FRS ß-subunit) and other proteins (Arc1p, Trbp111, EF-1ß and EF-1).

View larger version (27K): [in a new window]   Fig. 3. A schematic hypothetical model for the organization of mammalian, yeast and archea tRNA synthetase complexes. (A) The two-dimensional arrangement of the components in the mammalian multi-ARS synthetase complex. p38 is a scaffold protein for the assembly of the components. Some of the interactions, which have been determined by two-hybrid analyses (Rho et al., 1996; Quevillon et al., 1999) and crosslinking methods (Norcum and Warrington, 1998), are shown as arrows in this diagram. Owing to the limits of two-dimensional display, some interactions are not shown. (B) The yeast ARS complex consisting of two ARSs (MRS and ERS) and Arc1p, the yeast homolog of mammalian p43. Both ARSs interact directly with the N-terminal domain of Arc1p through their N-terminal appended domains (Galani et al., 2001). (C) The putative metabolic protein Mj1338 copurified with PRS from Methanococcus jannaschii interacts with KRSs from human and Methanobacterium thermoautotropicum in pull-down assays. Its interaction with DRS was also confirmed through identification of aminoacylation activity in a DEAE fraction obtained from total cell lysate of M. jannaschii (Lipman et al., 2000; Lipman et al., 2003). Although some components in these complexes have the potential for homodimerization, for simplicity this is not shown. The spatial arrangements and sizes of the components do not necessarily reflect their relative positions in the complexes.

View larger version (13K): [in a new window]   Fig. 4. The three-dimensional structure of trans- and cis-acting tRNA-binding domains present in ARSs and ARS-associated factors. (A) The peptides A147 to E314 of p43 (Kim, Y. et al., 2000; Renault et al., 2001) and M1 to A111 of Trbp111 (Morales et al., 1999). Two domains contain the typical oligonucleotide-binding (OB) fold, consisting of a five-stranded ß-barrel that is known to have RNA-binding capability. (B) The 57 aa peptide region from D677 to P733 of human EPRS (Cahuzac et al., 2000; Jeong et al., 2000). Notice that the basic residues are exposed from the two helices arranged in anti-parallel mode.

View larger version (31K): [in a new window]   Fig. 5. Three hypothetical models for dynamic movement of complex components. In the concerted model, all the components associate and dissociate simultaneously. In the partial association/dissociation model, each component associates or dissociates on an individual basis. In this case, there would be several different subcomplexes. In the static model, each component would be synthesized whenever necessary for other activities. In this case, the complex would be maintained stably once it is formed.