PMID- 19664639
OWN - NLM
STAT- MEDLINE
DCOM- 20091009
LR  - 20211020
IS  - 1089-8638 (Electronic)
IS  - 0022-2836 (Print)
IS  - 0022-2836 (Linking)
VI  - 393
IP  - 1
DP  - 2009 Oct 16
TI  - Crystal structure of the frizzled-like cysteine-rich domain of the receptor 
      tyrosine kinase MuSK.
PG  - 1-9
LID - 10.1016/j.jmb.2009.07.091 [doi]
AB  - Muscle-specific kinase (MuSK) is an essential receptor tyrosine kinase for the 
      establishment and maintenance of the neuromuscular junction (NMJ). Activation of 
      MuSK by agrin, a neuronally derived heparan-sulfate proteoglycan, and LRP4 
      (low-density lipoprotein receptor-related protein-4), the agrin receptor, leads 
      to clustering of acetylcholine receptors on the postsynaptic side of the NMJ. The 
      ectodomain of MuSK comprises three immunoglobulin-like domains and a 
      cysteine-rich domain (Fz-CRD) related to those in Frizzled proteins, the 
      receptors for Wnts. Here, we report the crystal structure of the MuSK Fz-CRD at 
      2.1 A resolution. The structure reveals a five-disulfide-bridged domain similar 
      to CRDs of Frizzled proteins but with a divergent C-terminal region. An 
      asymmetric dimer present in the crystal structure implicates surface hydrophobic 
      residues that may function in homotypic or heterotypic interactions to mediate 
      co-clustering of MuSK, rapsyn, and acetylcholine receptors at the NMJ.
FAU - Stiegler, Amy L
AU  - Stiegler AL
AD  - Structural Biology Program, Kimmel Center for Biology and Medicine of the 
      Skirball Institute, New York University School of Medicine, New York, NY 10016, 
      USA.
FAU - Burden, Steven J
AU  - Burden SJ
FAU - Hubbard, Stevan R
AU  - Hubbard SR
LA  - eng
SI  - PDB/3HKL
GR  - R01 NS027963-11/NS/NINDS NIH HHS/United States
GR  - R01 NS036193/NS/NINDS NIH HHS/United States
GR  - R01 NS053414-04/NS/NINDS NIH HHS/United States
GR  - T32 GM066704/GM/NIGMS NIH HHS/United States
GR  - R01 NS053414/NS/NINDS NIH HHS/United States
GR  - R01 NS027963/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090804
PL  - Netherlands
TA  - J Mol Biol
JT  - Journal of molecular biology
JID - 2985088R
RN  - 0 (Disulfides)
RN  - 0 (Receptors, Cholinergic)
RN  - EC 2.7.10.1 (MuSK protein, rat)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Crystallography, X-Ray
MH  - Dimerization
MH  - Disulfides
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Protein Structure, Quaternary
MH  - Protein Structure, Tertiary
MH  - Rats
MH  - Receptor Protein-Tyrosine Kinases/*chemistry
MH  - Receptors, Cholinergic/*chemistry
MH  - Sequence Alignment
PMC - PMC2754272
MID - NIHMS143106
EDAT- 2009/08/12 09:00
MHDA- 2009/10/10 06:00
PMCR- 2010/10/16
CRDT- 2009/08/12 09:00
PHST- 2009/05/27 00:00 [received]
PHST- 2009/07/26 00:00 [revised]
PHST- 2009/07/30 00:00 [accepted]
PHST- 2009/08/12 09:00 [entrez]
PHST- 2009/08/12 09:00 [pubmed]
PHST- 2009/10/10 06:00 [medline]
PHST- 2010/10/16 00:00 [pmc-release]
AID - S0022-2836(09)00980-2 [pii]
AID - 10.1016/j.jmb.2009.07.091 [doi]
PST - ppublish
SO  - J Mol Biol. 2009 Oct 16;393(1):1-9. doi: 10.1016/j.jmb.2009.07.091. Epub 2009 Aug 
      4.