3BJU

Crystal Structure of tetrameric form of human lysyl-tRNA synthetase

Summary for 3BJU

• Entry DOI: 10.2210/pdb3bju/pdb
• Descriptor: Lysyl-tRNA synthetase, CALCIUM ION, LYSINE, ... (5 entities in total)
• Functional Keywords: trna synthetase, lysyl-trna, aminoacyl-trna synthetase, atp-binding, cytoplasm, ligase, nucleotide-binding, phosphoprotein, polymorphism, protein biosynthesis
• Biological source: Homo sapiens (human)
• Cellular location: Isoform Cytoplasmic: Cytoplasm, cytosol . Isoform Mitochondrial: Mitochondrion : Q15046
• Total number of polymer chains: 4
• Total formula weight: 244343.64

Authors

Guo, M.,Yang, X.L.,Schimmel, P. (deposition date: 2007-12-04, release date: 2008-02-05, Last modification date: 2023-08-30)

Primary citation

Guo, M.,Ignatov, M.,Musier-Forsyth, K.,Schimmel, P.,Yang, X.L.
Crystal structure of tetrameric form of human lysyl-tRNA synthetase: Implications for multisynthetase complex formation
Proc.Natl.Acad.Sci.Usa, 105:2331-2336, 2008

PubMed Abstract: In mammals, many aminoacyl-tRNA synthetases are bound together in a multisynthetase complex (MSC) as a reservoir of procytokines and regulation molecules for functions beyond aminoacylation. The alpha(2) homodimeric lysyl-tRNA synthetase (LysRS) is tightly bound in the MSC and, under specific conditions, is secreted to trigger a proinflammatory response. Results by others suggest that alpha(2) LysRS is tightly bound into the core of the MSC with homodimeric beta(2) p38, a scaffolding protein that itself is multifunctional. Not understood is how the two dimeric proteins combine to make a presumptive alpha(2)beta(2) heterotetramer and, in particular, the location of the surfaces on LysRS that would accommodate the p38 interactions. Here we present a 2.3-A crystal structure of a tetrameric form of human LysRS. The relatively loose (as seen in solution) tetramer interface is assembled from two eukaryote-specific sequences, one in the catalytic- and another in the anticodon-binding domain. This same interface is predicted to provide unique determinants for interaction with p38. The analyses suggest how the core of the MSC is assembled and, more generally, that interactions and functions of synthetases can be built and regulated through dynamic protein-protein interfaces. These interfaces are created from small adaptations to what is otherwise a highly conserved (through evolution) polypeptide sequence.

PubMed: 18272479
DOI: 10.1073/pnas.0712072105

Experimental method

X-RAY DIFFRACTION (2.31 Å)