Abstract
In animal cells, nine aminoacyl-tRNA synthetases are associated with the three auxiliary proteins p18, p38, and p43 to form a stable and conserved large multi-aminoacyl-tRNA synthetase complex (MARS), whose molecular mass has been proposed to be between 1.0 and 1.5 MDa. The complex acts as a molecular hub for coordinating protein synthesis and diverse regulatory signal pathways. Electron microscopy studies defined its low resolution molecular envelope as an overall rather compact, asymmetric triangular shape. Here, we have analyzed the composition and homogeneity of the native mammalian MARS isolated from rabbit liver and characterized its overall internal structure, size, and shape at low resolution by hydrodynamic methods and small-angle x-ray scattering in solution. Our data reveal that the MARS exhibits a much more elongated and multi-armed shape than expected from previous reports. The hydrodynamic and structural features of the MARS are large compared with other supramolecular assemblies involved in translation, including ribosome. The large dimensions and non-compact structural organization of MARS favor a large protein surface accessibility for all its components. This may be essential to allow structural rearrangements between the catalytic and cis-acting tRNA binding domains of the synthetases required for binding the bulky tRNA substrates. This non-compact architecture may also contribute to the spatiotemporal controlled release of some of its components, which participate in non-canonical functions after dissociation from the complex.
Highlights
In animal cells, nine aminoacyl-tRNA synthetases form a supramolecular assembly
With a Rh, radius of gyration (Rg), and Dmax above 120, 135, and 450 Å, respectively, multi-aminoacyl-tRNA synthetase complex (MARS) displays large overall hydrodynamic and structural features for a supramolecular assembly involved in translation
These values are for example larger than those predicted from known crystal structures of prokaryotic large 50 S ribosomal subunits of ϳ1.5 MDa or their 70 S assembly of ϳ2.5 MDa, where Dmax values do not extend beyond 270 and 290 Å, respectively (Table 2)
Summary
Nine aminoacyl-tRNA synthetases form a supramolecular assembly. Results: The low resolution solution structure of this complex is determined by SAXS. Conclusion: This complex exhibits a non-compact, elongated, and multi-armed shape. The large dimensions and noncompact structural organization of MARS favor a large protein surface accessibility for all its components. This may be essential to allow structural rearrangements between the catalytic and cis-acting tRNA binding domains of the synthetases required for binding the bulky tRNA substrates. This non-compact architecture may contribute to the spatiotemporal controlled release of some of its components, which participate in noncanonical functions after dissociation from the complex
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