7dc3
Crystal structure of the MyRF ICA domain
Structural highlights
Publication Abstract from PubMedMyelin 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-beta-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 beta-helical stalk, determined at 2.4A resolution. The structure showed that its upstream beta-helical stalk is different from the triple beta-helix reported before. This is the first structure of the mammalian protein with a triple beta-helix. Structure analysis demonstrated that the triple alpha-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 beta-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. Crystal structure of the MyRF ICA domain with its upstream beta-helical stalk reveals the molecular mechanisms underlying its trimerization and self-cleavage.,Wu P, Zhen X, Li B, Yu Q, Huang X, Shi N Int J Biol Sci. 2021 Jul 13;17(11):2931-2943. doi: 10.7150/ijbs.57673., eCollection 2021. PMID:34345217[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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