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PDBsum entry 3ml4
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Signaling protein
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PDB id
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3ml4
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Contents |
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* Residue conservation analysis
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PDB id:
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| Name: |
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Signaling protein
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Title:
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Crystal structure of a complex between dok7 ph-ptb and the musk juxtamembrane region
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Structure:
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Protein dok-7. Chain: a, b, c, d. Fragment: unp residues 1-220. Synonym: downstream of tyrosine kinase 7. Engineered: yes. Muscle, skeletal receptor tyrosine-protein kinase. Chain: e, f, g, h. Fragment: unp residues 544-556. Synonym: muscle-specific tyrosine-protein kinase receptor, muscle-
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Source:
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Mus musculus. Mouse. Organism_taxid: 10090. Gene: dok7. Expressed in: escherichia coli. Expression_system_taxid: 469008. Synthetic: yes. Other_details: peptide (12mer)
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Resolution:
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2.60Å
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R-factor:
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0.255
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R-free:
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0.302
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Authors:
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E.Bergamin,S.R.Hubbard
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Key ref:
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E.Bergamin
et al.
(2010).
The cytoplasmic adaptor protein Dok7 activates the receptor tyrosine kinase MuSK via dimerization.
Mol Cell,
39,
100-109.
PubMed id:
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Date:
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16-Apr-10
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Release date:
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14-Jul-10
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PROCHECK
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Headers
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References
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Q18PE0
(DOK7_MOUSE) -
Protein Dok-7 from Mus musculus
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Seq:
Struc:
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504 a.a.
205 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Mol Cell
39:100-109
(2010)
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PubMed id:
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The cytoplasmic adaptor protein Dok7 activates the receptor tyrosine kinase MuSK via dimerization.
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E.Bergamin,
P.T.Hallock,
S.J.Burden,
S.R.Hubbard.
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ABSTRACT
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Formation of the vertebrate neuromuscular junction requires, among others
proteins, Agrin, a neuronally derived ligand, and the following muscle proteins:
LRP4, the receptor for Agrin; MuSK, a receptor tyrosine kinase (RTK); and Dok7
(or Dok-7), a cytoplasmic adaptor protein. Dok7 comprises a pleckstrin-homology
(PH) domain, a phosphotyrosine-binding (PTB) domain, and C-terminal sites of
tyrosine phosphorylation. Unique among adaptor proteins recruited to RTKs, Dok7
is not only a substrate of MuSK, but also an activator of MuSK's kinase
activity. Here, we present the crystal structure of the Dok7 PH-PTB domains in
complex with a phosphopeptide representing the Dok7-binding site on MuSK. The
structure and biochemical data reveal a dimeric arrangement of Dok7 PH-PTB that
facilitates trans-autophosphorylation of the kinase activation loop. The
structure provides the molecular basis for MuSK activation by Dok7 and for
rationalizing several Dok7 loss-of-function mutations found in patients with
congenital myasthenic syndromes.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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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.
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Int J Biochem Cell Biol,
43,
295-298.
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A.Bill,
A.Schmitz,
B.Albertoni,
J.N.Song,
L.C.Heukamp,
D.Walrafen,
F.Thorwirth,
P.J.Verveer,
S.Zimmer,
L.Meffert,
A.Schreiber,
S.Chatterjee,
R.K.Thomas,
R.T.Ullrich,
T.Lang,
and
M.Famulok
(2010).
Cytohesins are cytoplasmic ErbB receptor activators.
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Cell,
143,
201-211.
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B.Z.Shilo
(2010).
Insider influence on ErbB activity.
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Cell,
143,
181-182.
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D.G.Metcalf,
D.T.Moore,
Y.Wu,
J.M.Kielec,
K.Molnar,
K.G.Valentine,
A.J.Wand,
J.S.Bennett,
and
W.F.DeGrado
(2010).
NMR analysis of the alphaIIb beta3 cytoplasmic interaction suggests a mechanism for integrin regulation.
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Proc Natl Acad Sci U S A,
107,
22481-22486.
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PDB code:
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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
code is
shown on the right.
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Links
