Dok7 is a cytoplasmic adaptor protein that contains tandem PH and PTB domains in the N-terminal portion of the molecule. In muscle, Dok7 is required for MuSK activation, and the structure of the PH and PTB domains revealed that these domains form a dimer that binds to the juxtamembrane phosphotyrosine (pY553) in MuSK, facilitating phosphorylation of the kinase activation loop.


Model for the activation of MuSK by Dok7. The protomers of the Dok7 PH-PTB dimer are colored orange and yellow, and the two tyrosine kinase domains of the MuSK dimer are colored light and dark green. Phosphorylated Y553 is shown in sphere representation and colored red. [Bergamin et al., Mol. Cell 38, 100-109 (2010)]