A Bacteriophage Tailspike Domain Promotes Self-Cleavage of a Human Membrane-Bound Transcription Factor, the Myelin Regulatory Factor MYRF

• DOI: 10.1371/journal.pbio.1001624
• Publication Date: 2013-08-13T16:44:24Z
• Authors: Zhihua Li; Yungki Park; Edward M. Marcotte
• Keywords: Chaperone (clinical); Proteolysis

Myelination of the central nervous system (CNS) is critical to vertebrate systems for efficient neural signaling. CNS myelination occurs as oligodendrocytes terminally differentiate, a process regulated in part by myelin regulatory factor, MYRF. Using bioinformatics and extensive biochemical functional assays, we find that MYRF generated an integral membrane protein must be processed release its transcription factor domain from membrane. In contrast most membrane-bound factors, proteolysis seems constitutive independent cell- tissue-type, demonstrate reconstitution E. coli yeast. The apparent absence physiological cues raises question how why processed. By using computational methods capable recognizing extremely divergent sequence homology, identified distantly related bacteriophage tailspike proteins. Although occurring otherwise unrelated proteins, phage domains are known chaperone proteins' trimerization auto-cleavage, raising hypothesis might contribute novel activation method factor. We indeed serves intramolecular facilitates proteolysis. Functional assays confirm domain-mediated auto-proteolysis essential both MYRF's transcriptional activity ability promote oligodendrocyte maturation. This work thus reveals previously unknown key step myelination. These data also reconcile conflicting observations this family, different members which have been transmembrane or nuclear Finally, our illustrate remarkable evolutionary repurposing between bacteriophages eukaryotes, with catalyzing trimerization-dependent two entirely distinct cellular contexts, one case participating maturation other activating