4DPG

Crystal Structure of Human LysRS: P38/AIMP2 Complex I


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.84 Å
  • R-Value Free: 0.223 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.187 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Structural Switch of Lysyl-tRNA Synthetase between Translation and Transcription.

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.

(2013) Mol Cell 49: 30-42

  • DOI: https://doi.org/10.1016/j.molcel.2012.10.010
  • Primary Citation of Related Structures:  
    4DPG

  • 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.


  • Organizational Affiliation

    Department of Biochemistry and Molecular Biology, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Lysine--tRNA ligase
A, B, C, D, E
A, B, C, D, E, F, G, H
513Homo sapiensMutation(s): 0 
Gene Names: KARSKIAA0070
EC: 6.1.1.6
UniProt & NIH Common Fund Data Resources
Find proteins for Q15046 (Homo sapiens)
Explore Q15046 
Go to UniProtKB:  Q15046
PHAROS:  Q15046
GTEx:  ENSG00000065427 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ15046
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Aminoacyl tRNA synthase complex-interacting multifunctional protein 2
I, J, K, L
54Homo sapiensMutation(s): 0 
Gene Names: AIMP2JTV1PRO0992
UniProt & NIH Common Fund Data Resources
Find proteins for Q13155 (Homo sapiens)
Explore Q13155 
Go to UniProtKB:  Q13155
PHAROS:  Q13155
GTEx:  ENSG00000106305 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13155
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
APC
Query on APC

Download Ideal Coordinates CCD File 
CA [auth F]
GA [auth G]
KA [auth H]
N [auth A]
Q [auth B]
CA [auth F],
GA [auth G],
KA [auth H],
N [auth A],
Q [auth B],
T [auth C],
W [auth D],
Z [auth E]
DIPHOSPHOMETHYLPHOSPHONIC ACID ADENOSYL ESTER
C11 H18 N5 O12 P3
CAWZRIXWFRFUQB-IOSLPCCCSA-N
LYS
Query on LYS

Download Ideal Coordinates CCD File 
BA [auth F]
FA [auth G]
JA [auth H]
M [auth A]
P [auth B]
BA [auth F],
FA [auth G],
JA [auth H],
M [auth A],
P [auth B],
S [auth C],
V [auth D],
Y [auth E]
LYSINE
C6 H15 N2 O2
KDXKERNSBIXSRK-YFKPBYRVSA-O
ALA
Query on ALA

Download Ideal Coordinates CCD File 
IA [auth H]ALANINE
C3 H7 N O2
QNAYBMKLOCPYGJ-REOHCLBHSA-N
MG
Query on MG

Download Ideal Coordinates CCD File 
AA [auth E]
DA [auth F]
EA [auth F]
HA [auth G]
LA [auth H]
AA [auth E],
DA [auth F],
EA [auth F],
HA [auth G],
LA [auth H],
MA [auth H],
NA [auth J],
O [auth A],
OA [auth L],
R [auth B],
U [auth C],
X [auth D]
MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.84 Å
  • R-Value Free: 0.223 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.187 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 79.2α = 89.16
b = 122.01β = 85.58
c = 149.2γ = 89.71
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
MAR345dtbdata collection
HKL-2000data reduction
HKL-2000data scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-02-13
    Type: Initial release
  • Version 1.1: 2017-11-15
    Changes: Refinement description
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations