PMID- 17011580
OWN - NLM
STAT- MEDLINE
DCOM- 20070116
LR  - 20181227
IS  - 0022-2836 (Print)
IS  - 1089-8638 (Electronic)
IS  - 0022-2836 (Linking)
VI  - 364
IP  - 3
DP  - 2006 Dec 1
TI  - Crystal structure of the agrin-responsive immunoglobulin-like domains 1 and 2 of 
      the receptor tyrosine kinase MuSK.
PG  - 424-33
AB  - Muscle-specific kinase (MuSK) is a receptor tyrosine kinase expressed exclusively 
      in skeletal muscle, where it is required for formation of the neuromuscular 
      junction. MuSK is activated by agrin, a neuron-derived heparan sulfate 
      proteoglycan. Here, we report the crystal structure of the agrin-responsive first 
      and second immunoglobulin-like domains (Ig1 and Ig2) of the MuSK ectodomain at 
      2.2 A resolution. The structure reveals that MuSK Ig1 and Ig2 are Ig-like domains 
      of the I-set subfamily, which are configured in a linear, semi-rigid arrangement. 
      In addition to the canonical internal disulfide bridge, Ig1 contains a second, 
      solvent-exposed disulfide bridge, which our biochemical data indicate is critical 
      for proper folding of Ig1 and processing of MuSK. Two Ig1-2 molecules form a 
      non-crystallographic dimer that is mediated by a unique hydrophobic patch on the 
      surface of Ig1. Biochemical analyses of MuSK mutants introduced into MuSK(-/-) 
      myotubes demonstrate that residues in this hydrophobic patch are critical for 
      agrin-induced MuSK activation.
FAU - Stiegler, Amy L
AU  - Stiegler AL
AD  - Structural Biology Program, Skirball Institute of Biomolecular Medicine and 
      Department of Pharmacology, 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/2IEP
GR  - R37 NS036193/NS/NINDS NIH HHS/United States
GR  - NS036193/NS/NINDS NIH HHS/United States
GR  - R01 NS036193/NS/NINDS NIH HHS/United States
GR  - R01 NS036193-09/NS/NINDS NIH HHS/United States
GR  - R01 NS053414/NS/NINDS NIH HHS/United States
GR  - NS053414/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060912
PL  - Netherlands
TA  - J Mol Biol
JT  - Journal of molecular biology
JID - 2985088R
RN  - 0 (Agrin)
RN  - 0 (Immunoglobulins)
RN  - 0 (Receptors, Cholinergic)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.10.1 (MuSK protein, rat)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Agrin/*chemistry
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Cell Line
MH  - Immunoglobulins/*chemistry
MH  - *Models, Molecular
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Protein Folding
MH  - Protein Structure, Tertiary
MH  - Rats
MH  - Receptor Protein-Tyrosine Kinases/*chemistry/genetics
MH  - Receptors, Cholinergic/*chemistry/genetics
MH  - Recombinant Proteins/chemistry/genetics
PMC - PMC1752213
MID - NIHMS14115
EDAT- 2006/10/03 09:00
MHDA- 2007/01/17 09:00
PMCR- 2008/01/30
CRDT- 2006/10/03 09:00
PHST- 2006/06/13 00:00 [received]
PHST- 2006/08/30 00:00 [revised]
PHST- 2006/09/05 00:00 [accepted]
PHST- 2006/10/03 09:00 [pubmed]
PHST- 2007/01/17 09:00 [medline]
PHST- 2006/10/03 09:00 [entrez]
PHST- 2008/01/30 00:00 [pmc-release]
AID - S0022-2836(06)01208-3 [pii]
AID - 10.1016/j.jmb.2006.09.019 [doi]
PST - ppublish
SO  - J Mol Biol. 2006 Dec 1;364(3):424-33. doi: 10.1016/j.jmb.2006.09.019. Epub 2006 
      Sep 12.