Hedgehog Regulates Smoothened Activity by Inducing a Conformational Switch  

Oleh:

Yun, Zhao ; Chao, Tong ; Jiang, Jin

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: NATURE (keterangan: ada di Proquest) vol. 450 no. 7167 (Nov. 2007), page 252.

Ketersediaan

Perpustakaan FK Nomor Panggil: N01.K.2007.10 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

Lihat Detail Induk

Isi artikel

Hedgehog (HH) morphogen is essential for metazoan development. The seven-transmembrane protein smoothened (SMO) transduces tha HH signal across the plasma membrane, but how SMO is activated remains poorly understood . In Dorsophila melanogaster, HH induces phosphorylation at multiple Ser/Thr residues in the SMO carboxy-terminal cytoplasmic tail, leading to its cell surface accumulation and activation. Here we provide evidence that phosphorylation activates. SMO by inducing a conformational switch. This occurs by antagonizing multiple Arg clusters in the SMO cytoplasmic tail. The Arg cluster inhibits SMO by blocking its cell surface expression and keeping it in an inactive conformation that is maintened by intramolecular electrosattic interactions. HH-induced phosphorylation distrups the interaction, and induces a conformational switch and dimerization of SMO cytoplasmic tails, which is essential for pathway activation. Increasing the number of mutations in the Arg clusters progressively activates SMO. Hence, by employing multiple Arg clusters as inhibitory elements counteracted by differential phosphorylation, SMO acts as a rheostat to translate graded HH signal into distinct responses.

Opini Anda

Klik untuk menuliskan opini Anda tentang koleksi ini!

Kembali