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PDBsum entry 1luf

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protein links
Transferase PDB id
1luf
Jmol
Contents
Protein chain
275 a.a. *
Waters ×114
* Residue conservation analysis
PDB id:
1luf
Name: Transferase
Title: Crystal structure of the musk tyrosine kinase: insights into receptor autoregulation
Structure: Muscle-specific tyrosine kinase receptor musk. Chain: a. Fragment: cytoplasmic region (residues 526-868). Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
2.05Å     R-factor:   0.231     R-free:   0.246
Authors: J.H.Till,M.Becerra,A.Watty,Y.Lu,Y.Ma,T.A.Neubert,S.J.Burden, S.R.Hubbard
Key ref:
J.H.Till et al. (2002). Crystal structure of the MuSK tyrosine kinase: insights into receptor autoregulation. Structure, 10, 1187-1196. PubMed id: 12220490 DOI: 10.1016/S0969-2126(02)00814-6
Date:
22-May-02     Release date:   11-Sep-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q62838  (MUSK_RAT) -  Muscle, skeletal receptor tyrosine protein kinase
Seq:
Struc:
 
Seq:
Struc:
868 a.a.
275 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.7.10.1  - Receptor protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
ATP
+ [protein]-L-tyrosine
= ADP
+ [protein]-L-tyrosine phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     protein phosphorylation   1 term 
  Biochemical function     transferase activity, transferring phosphorus-containing groups     4 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(02)00814-6 Structure 10:1187-1196 (2002)
PubMed id: 12220490  
 
 
Crystal structure of the MuSK tyrosine kinase: insights into receptor autoregulation.
J.H.Till, M.Becerra, A.Watty, Y.Lu, Y.Ma, T.A.Neubert, S.J.Burden, S.R.Hubbard.
 
  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.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Overall Structure of the MuSK Cytoplasmic Domain(A) A ribbon diagram of the MuSK crystal structure, with b strands (numbered) shown in cyan and a helices (lettered) shown in red. The juxtamembrane segment (N terminal) and the activation loop (containing aAL) are colored green. The activation loop tyrosines, Tyr-750/754/755, are shown in ball and stick representation (black).(B) A stereo view of a Ca trace of MuSK in the same orientation as the diagram in (A). Every 10th residue is marked with a closed circle, and every 20th residue is labeled with the residue number.
 
  The above figure is reprinted by permission from Cell Press: Structure (2002, 10, 1187-1196) copyright 2002.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21255125 A.R.Punga, M.Maj, S.Lin, S.Meinen, and M.A.Rüegg (2011).
MuSK levels differ between adult skeletal muscles and influence postsynaptic plasticity.
  Eur J Neurosci, 33, 890-898.  
20974278 N.Ghazanfari, K.J.Fernandez, Y.Murata, M.Morsch, S.T.Ngo, S.W.Reddel, P.G.Noakes, and W.D.Phillips (2011).
Muscle specific kinase: organiser of synaptic membrane domains.
  Int J Biochem Cell Biol, 43, 295-298.  
20632993 C.C.Lee, Y.Jia, N.Li, X.Sun, K.Ng, E.Ambing, M.Y.Gao, S.Hua, C.Chen, S.Kim, P.Y.Michellys, S.A.Lesley, J.L.Harris, and G.Spraggon (2010).
Crystal structure of the ALK (anaplastic lymphoma kinase) catalytic domain.
  Biochem J, 430, 425-437.
PDB codes: 3l9p 3lcs 3lct
20603078 E.Bergamin, P.T.Hallock, S.J.Burden, and S.R.Hubbard (2010).
The cytoplasmic adaptor protein Dok7 activates the receptor tyrosine kinase MuSK via dimerization.
  Mol Cell, 39, 100-109.
PDB code: 3ml4
20351256 F.Shi, S.E.Telesco, Y.Liu, R.Radhakrishnan, and M.A.Lemmon (2010).
ErbB3/HER3 intracellular domain is competent to bind ATP and catalyze autophosphorylation.
  Proc Natl Acad Sci U S A, 107, 7692-7697.
PDB code: 3lmg
20003389 B.S.Lipska, E.Drozynska, P.Scaruffi, G.P.Tonini, E.Izycka-Swieszewska, S.Zietkiewicz, A.Balcerska, D.Perek, A.Chybicka, W.Biernat, and J.Limon (2009).
c.1810C>T polymorphism of NTRK1 gene is associated with reduced survival in neuroblastoma patients.
  BMC Cancer, 9, 436.  
19274663 C.W.Ward, and M.C.Lawrence (2009).
Ligand-induced activation of the insulin receptor: a multi-step process involving structural changes in both the ligand and the receptor.
  Bioessays, 31, 422-434.  
19224897 E.D.Lew, C.M.Furdui, K.S.Anderson, and J.Schlessinger (2009).
The precise sequence of FGF receptor autophosphorylation is kinetically driven and is disrupted by oncogenic mutations.
  Sci Signal, 2, ra6.  
19618435 S.T.Lee, J.Lee, M.Lee, J.W.Kim, and C.S.Ki (2009).
Clinical and genetic analysis of Korean patients with congenital insensitivity to pain with anhidrosis.
  Muscle Nerve, 40, 855-859.  
17586502 B.P.Craddock, C.Cotter, and W.T.Miller (2007).
Autoinhibition of the insulin-like growth factor I receptor by the juxtamembrane region.
  FEBS Lett, 581, 3235-3240.  
17649979 C.O.Sallum, R.A.Kammerer, and A.T.Alexandrescu (2007).
Thermodynamic and structural studies of carbohydrate binding by the agrin-G3 domain.
  Biochemistry, 46, 9541-9550.  
17452444 N.Jones, W.R.Hardy, M.B.Friese, C.Jorgensen, M.J.Smith, N.M.Woody, S.J.Burden, and T.Pawson (2007).
Analysis of a Shc family adaptor protein, ShcD/Shc4, that associates with muscle-specific kinase.
  Mol Cell Biol, 27, 4759-4773.  
16507368 C.M.Furdui, E.D.Lew, J.Schlessinger, and K.S.Anderson (2006).
Autophosphorylation of FGFR1 kinase is mediated by a sequential and precisely ordered reaction.
  Mol Cell, 21, 711-717.  
16146773 N.Rahimi (2006).
VEGFR-1 and VEGFR-2: two non-identical twins with a unique physiognomy.
  Front Biosci, 11, 818-829.  
16713597 N.Rahimi (2006).
Vascular endothelial growth factor receptors: molecular mechanisms of activation and therapeutic potentials.
  Exp Eye Res, 83, 1005-1016.  
16818610 T.Cheusova, M.A.Khan, S.W.Schubert, A.C.Gavin, T.Buchou, G.Jacob, H.Sticht, J.Allende, B.Boldyreff, H.R.Brenner, and S.Hashemolhosseini (2006).
Casein kinase 2-dependent serine phosphorylation of MuSK regulates acetylcholine receptor aggregation at the neuromuscular junction.
  Genes Dev, 20, 1800-1816.  
16244704 E.D.Scheeff, and P.E.Bourne (2005).
Structural evolution of the protein kinase-like superfamily.
  PLoS Comput Biol, 1, e49.  
16040609 J.P.Vainonen, M.Hansson, and A.V.Vener (2005).
STN8 protein kinase in Arabidopsis thaliana is specific in phosphorylation of photosystem II core proteins.
  J Biol Chem, 280, 33679-33686.  
15632155 N.Yokoyama, I.Ischenko, M.J.Hayman, and W.T.Miller (2005).
The C terminus of RON tyrosine kinase plays an autoinhibitory role.
  J Biol Chem, 280, 8893-8900.  
15123710 C.D.Mol, D.R.Dougan, T.R.Schneider, R.J.Skene, M.L.Kraus, D.N.Scheibe, G.P.Snell, H.Zou, B.C.Sang, and K.P.Wilson (2004).
Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase.
  J Biol Chem, 279, 31655-31663.
PDB codes: 1t45 1t46
15297464 C.M.Rohde, J.Schrum, and A.W.Lee (2004).
A juxtamembrane tyrosine in the colony stimulating factor-1 receptor regulates ligand-induced Src association, receptor kinase function, and down-regulation.
  J Biol Chem, 279, 43448-43461.  
15308621 J.C.Lougheed, R.H.Chen, P.Mak, and T.J.Stout (2004).
Crystal structures of the phosphorylated and unphosphorylated kinase domains of the Cdc42-associated tyrosine kinase ACK1.
  J Biol Chem, 279, 44039-44045.
PDB codes: 1u46 1u4d 1u54
14759363 J.Griffith, J.Black, C.Faerman, L.Swenson, M.Wynn, F.Lu, J.Lippke, and K.Saxena (2004).
The structural basis for autoinhibition of FLT3 by the juxtamembrane domain.
  Mol Cell, 13, 169-178.
PDB code: 1rjb
15173825 S.R.Hubbard (2004).
Juxtamembrane autoinhibition in receptor tyrosine kinases.
  Nat Rev Mol Cell Biol, 5, 464-471.  
12707268 S.Li, N.D.Covino, E.G.Stein, J.H.Till, and S.R.Hubbard (2003).
Structural and biochemical evidence for an autoinhibitory role for tyrosine 984 in the juxtamembrane region of the insulin receptor.
  J Biol Chem, 278, 26007-26014.
PDB code: 1p14
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.