7DC3

Crystal structure of the MyRF ICA domain

7DC3 の概要

• エントリーDOI: 10.2210/pdb7dc3/pdb
• 分子名称: Isoform 2 of Myelin regulatory factor (2 entities in total)
• 機能のキーワード: auto-catalytic protease, protein chaperone. trimeric protein, triple coiled-coil, membrane protein
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 61454.23

構造登録者

Shi, N.,Wu, P.,Zhen, X.K.,Li, B.W. (登録日: 2020-10-23, 公開日: 2021-08-25, 最終更新日: 2024-10-30)

主引用文献

Wu, P.,Zhen, X.,Li, B.,Yu, Q.,Huang, X.,Shi, N.
Crystal structure of the MyRF ICA domain with its upstream beta-helical stalk reveals the molecular mechanisms underlying its trimerization and self-cleavage.
Int J Biol Sci, 17:2931-2943, 2021

PubMed Abstract: Myelin gene regulatory factor (MyRF), a novel membrane transcription factor expressed on the endoplasmic reticulum membrane, functions as a trimer. The trimerization of MyRF is associated with a fragment between the DNA binding domain and transmembrane domain that shares homology with the triple-β-helix and intramolecular chaperone autocleavage (ICA) domain of phage tailspike proteins. The molecular details of these domains in eukaryotes have not been elucidated. Here, we present the crystal structure of the MyRF ICA domain with its upstream β-helical stalk, determined at 2.4Å resolution. The structure showed that its upstream β-helical stalk is different from the triple β-helix reported before. This is the first structure of the mammalian protein with a triple β-helix. Structure analysis demonstrated that the triple α-helical coiled-coil formed at the MyRF ICA domain C-terminal was the main driving force for the trimerization. Additionally, our findings showed that MyRF was cleaved via a highly conserved serine-lysine catalytic dyad mechanism and that cleavage would be activated only if the ICA domains were organized as trimers. In contrast to the viral ICA domain, almost no interaction was found between the MyRF ICA domain and its upstream neighboring β-helix of the stalk; thus, activation of self-cleavage may not be triggered by the upstream region of the ICA domain, contrary to the observations made in phages. These findings provided an important insight into the molecular mechanisms of MyRF trimerization and self-cleavage.

PubMed: 34345217
DOI: 10.7150/ijbs.57673

実験手法

X-RAY DIFFRACTION (2.4 Å)