1LUF

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

1LUF の概要

• エントリーDOI: 10.2210/pdb1luf/pdb
• 分子名称: muscle-specific tyrosine kinase receptor musk (2 entities in total)
• 機能のキーワード: phosphorylation, signal transduction, mass spectrometry, transferase
• 由来する生物種: Rattus norvegicus (Norway rat)
• 細胞内の位置: Cell junction, synapse, postsynaptic cell membrane ; Single-pass type I membrane protein : Q62838
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38754.66

構造登録者

Till, J.H.,Becerra, M.,Watty, A.,Lu, Y.,Ma, Y.,Neubert, T.A.,Burden, S.J.,Hubbard, S.R. (登録日: 2002-05-22, 公開日: 2002-09-11, 最終更新日: 2024-02-14)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.05 Å)