1LUF

Crystal Structure of the MuSK Tyrosine Kinase: Insights into Receptor Autoregulation


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.231 
  • R-Value Observed: 0.231 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Crystal structure of the MuSK tyrosine kinase: insights into receptor autoregulation.

Till, J.H.Becerra, M.Watty, A.Lu, Y.Ma, Y.Neubert, T.A.Burden, S.J.Hubbard, S.R.

(2002) Structure 10: 1187-1196

  • DOI: https://doi.org/10.1016/s0969-2126(02)00814-6
  • Primary Citation of Related Structures:  
    1LUF

  • PubMed Abstract: 

    Muscle-specific kinase (MuSK) is a receptor tyrosine kinase expressed selectively in skeletal muscle. During neuromuscular synapse formation, agrin released from motor neurons stimulates MuSK autophosphorylation in the kinase activation loop and in the juxtamembrane region, leading to clustering of acetylcholine receptors. We have determined the crystal structure of the cytoplasmic domain of unphosphorylated MuSK at 2.05 A resolution. The structure reveals an autoinhibited kinase domain in which the activation loop obstructs ATP and substrate binding. Steady-state kinetic analysis demonstrates that autophosphorylation results in a 200-fold increase in k(cat) and a 10-fold decrease in the K(m) for ATP. These studies provide a molecular basis for understanding the regulation of MuSK catalytic activity and suggest that an additional in vivo component may contribute to regulation via the juxtamembrane region.


  • Organizational Affiliation

    Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York university School of Medicine, New York, NY 10016, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
muscle-specific tyrosine kinase receptor musk343Rattus norvegicusMutation(s): 0 
EC: 2.7.1.112
UniProt
Find proteins for Q62838 (Rattus norvegicus)
Explore Q62838 
Go to UniProtKB:  Q62838
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ62838
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.231 
  • R-Value Observed: 0.231 
  • Space Group: I 4
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 146.939α = 90
b = 146.939β = 90
c = 39.017γ = 90
Software Package:
Software NamePurpose
AMoREphasing
CNSrefinement
MADNESSdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2002-09-11
    Type: Initial release
  • Version 1.1: 2008-04-28
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Advisory, Refinement description
  • Version 1.4: 2024-02-14
    Changes: Advisory, Data collection, Database references, Refinement description