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3bju

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3bju, resolution 2.31Å ()
Sites: , , , , , , , , , , , , , , , , , , and
Ligands: , ,
Gene: KARS, KIAA0070 (Homo sapiens)
Activity: Lysine--tRNA ligase, with EC number 6.1.1.6
Domains: LysU, LysRS_core, LysRS_N
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Crystal Structure of tetrameric form of human lysyl-tRNA synthetase

Publication Abstract from PubMed

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.

Crystal structure of tetrameric form of human lysyl-tRNA synthetase: Implications for multisynthetase complex formation., Guo M, Ignatov M, Musier-Forsyth K, Schimmel P, Yang XL, Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2331-6. Epub 2008 Feb 13. PMID:18272479

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

3BJU is a 4 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  • Guo M, Ignatov M, Musier-Forsyth K, Schimmel P, Yang XL. Crystal structure of tetrameric form of human lysyl-tRNA synthetase: Implications for multisynthetase complex formation. Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2331-6. Epub 2008 Feb 13. PMID:18272479

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