1LUF

Crystal Structure of the MuSK Tyrosine Kinase: Insights into Receptor Autoregulation

Summary for 1LUF

• Entry DOI: 10.2210/pdb1luf/pdb
• Descriptor: muscle-specific tyrosine kinase receptor musk (2 entities in total)
• Functional Keywords: phosphorylation, signal transduction, mass spectrometry, transferase
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Cell junction, synapse, postsynaptic cell membrane ; Single-pass type I membrane protein : Q62838
• Total number of polymer chains: 1
• Total formula weight: 38754.66

Authors

Till, J.H.,Becerra, M.,Watty, A.,Lu, Y.,Ma, Y.,Neubert, T.A.,Burden, S.J.,Hubbard, S.R. (deposition date: 2002-05-22, release date: 2002-09-11, Last modification date: 2024-02-14)

Primary citation

Till, J.H.,Becerra, M.,Watty, A.,Lu, Y.,Ma, Y.,Neubert, T.A.,Burden, S.J.,Hubbard, S.R.
Crystal structure of the MuSK tyrosine kinase: insights into receptor autoregulation.
Structure, 10:1187-1196, 2002

PubMed Abstract: 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.

PubMed: 12220490
DOI: 10.1016/S0969-2126(02)00814-6

Experimental method

X-RAY DIFFRACTION (2.05 Å)