1luf
From Proteopedia
Crystal Structure of the MuSK Tyrosine Kinase: Insights into Receptor Autoregulation
Overview
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.
About this Structure
1LUF is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
Crystal structure of the MuSK tyrosine kinase: insights into receptor autoregulation., Till JH, Becerra M, Watty A, Lu Y, Ma Y, Neubert TA, Burden SJ, Hubbard SR, Structure. 2002 Sep;10(9):1187-96. PMID:12220490 Page seeded by OCA on Sat May 3 00:17:58 2008
