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PDBsum entry 1luf
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the musk tyrosine kinase: insights into receptor autoregulation.
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Authors
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J.H.Till,
M.Becerra,
A.Watty,
Y.Lu,
Y.Ma,
T.A.Neubert,
S.J.Burden,
S.R.Hubbard.
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Ref.
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Structure, 2002,
10,
1187-1196.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2002,
10,
1187-1196)
copyright 2002.
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