4DPG

Crystal Structure of Human LysRS: P38/AIMP2 Complex I

Summary for 4DPG

• Entry DOI: 10.2210/pdb4dpg/pdb
• Related: 4DPJ
• Descriptor: Lysine--tRNA ligase, Aminoacyl tRNA synthase complex-interacting multifunctional protein 2, LYSINE, ... (7 entities in total)
• Functional Keywords: lysyl-trna synthetase, lysrs, p38, aimp2, multi trna synthetase complex sub-complex, ligase-apoptosis complex, ligase/apoptosis
• Biological source: Homo sapiens (human); More
• Cellular location: Isoform Cytoplasmic: Cytoplasm, cytosol . Isoform Mitochondrial: Mitochondrion : Q15046; Cytoplasm, cytosol : Q13155
• Total number of polymer chains: 12
• Total formula weight: 503812.56

Authors

Fang, P.,Wang, J.,Bennett, S.P.,Guo, M. (deposition date: 2012-02-13, release date: 2013-02-13, Last modification date: 2024-02-28)

Primary citation

Ofir-Birin, Y.,Fang, P.,Bennett, S.P.,Zhang, H.M.,Wang, J.,Rachmin, I.,Shapiro, R.,Song, J.,Dagan, A.,Pozo, J.,Kim, S.,Marshall, A.G.,Schimmel, P.,Yang, X.L.,Nechushtan, H.,Razin, E.,Guo, M.
Structural Switch of Lysyl-tRNA Synthetase between Translation and Transcription.
Mol.Cell, 49:30-42, 2013

PubMed Abstract: Lysyl-tRNA synthetase (LysRS), a component of the translation apparatus, is released from the cytoplasmic multi-tRNA synthetase complex (MSC) to activate the transcription factor MITF in stimulated mast cells through undefined mechanisms. Here we show that Ser207 phosphorylation provokes a new conformer of LysRS that inactivates its translational function but activates its transcriptional function. The crystal structure of an MSC subcomplex established that LysRS is held in the MSC by binding to the N terminus of the scaffold protein p38/AIMP2. Phosphorylation-created steric clashes at the LysRS domain interface disrupt its binding grooves for p38/AIMP2, releasing LysRS and provoking its nuclear translocation. This alteration also exposes the C-terminal domain of LysRS to bind to MITF and triggers LysRS-directed production of the second messenger Ap(4)A that activates MITF. Thus our results establish that a single conformational change triggered by phosphorylation leads to multiple effects driving an exclusive switch of LysRS function from translation to transcription.

PubMed: 23159739
DOI: 10.1016/j.molcel.2012.10.010

Experimental method

X-RAY DIFFRACTION (2.844 Å)