4dpg

Crystal Structure of Human LysRS: P38/AIMP2 Complex ICrystal Structure of Human LysRS: P38/AIMP2 Complex I

Structural highlights 4dpg is a 12 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , , Related: 4dpj Gene: KARS, KIAA0070 (Homo sapiens), AIMP2, JTV1, PRO0992 (Homo sapiens) Activity: Lysine--tRNA ligase, with EC number 6.1.1.6 Resources: FirstGlance, OCA, RCSB, PDBsum Disease [SYK_HUMAN] Defects in KARS are the cause of Charcot-Marie-Tooth disease recessive intermediate type B (CMTRIB) [MIM:613641]; also called Charcot-Marie-Tooth neuropathy recessive intermediate B. CMTRIB is a form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Recessive intermediate forms of Charcot-Marie-Tooth disease are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. Function [SYK_HUMAN] Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA. When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages. Catalyzes the synthesis of diadenosine oligophosphate (Ap4A), a signaling molecule involved in the activation of MITF transcriptional activity. Interacts with HIV-1 virus GAG protein, facilitating the selective packaging of tRNA(3)(Lys), the primer for reverse transcription initiation. [AIMP2_HUMAN] Required for assembly and stability of the aminoacyl-tRNA synthase complex. Mediates ubiquitination and degradation of FUBP1, a transcriptional activator of MYC, leading to MYC down-regulation which is required for aveolar type II cell differentiation. Blocks MDM2-mediated ubiquitination and degradation of p53/TP53. Functions as a proapoptotic factor. Publication Abstract from PubMed 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. Structural Switch of Lysyl-tRNA Synthetase between Translation and Transcription.,Ofir-Birin Y, Fang P, Bennett SP, Zhang HM, Wang J, Rachmin I, Shapiro R, Song J, Dagan A, Pozo J, Kim S, Marshall AG, Schimmel P, Yang XL, Nechushtan H, Razin E, Guo M Mol Cell. 2013 Jan 10;49(1):30-42. doi: 10.1016/j.molcel.2012.10.010. Epub 2012, Nov 15. PMID:23159739 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 4dpg, resolution 2.84Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image