Subunit-specific degradation of the UmuD/D′ heterodimer by the ClpXP protease: the role of trans recognition in UmuD′ stability

AUTOR(ES)

Gonzalez, Martín

FONTE

Oxford University Press

RESUMO

The Escherichia coli UmuD′ protein is a subunit of the recently described error-prone DNA polymerase, pol V. UmuD′ is initially synthesized as an unstable and mutagenically inactive pro-protein, UmuD. Upon processing, UmuD′ assumes a relatively stable conformation and becomes mutagenically active. While UmuD and UmuD′ by themselves exist in vivo as homodimers, when together they preferentially interact to form heterodimers. Quite strikingly, it is in this context that UmuD′ becomes susceptible to ClpXP-mediated proteolysis. Here we report a novel targeting mechanism designed for degrading the mutagenically active UmuD′ subunit of the UmuD/D′ heterodimer complex, while leaving the UmuD protein intact. Surprisingly, a signal that is essential and sufficient for targeting UmuD′ for degradation was found to reside on UmuD not UmuD′. UmuD was also shown to be capable of channeling an excess of UmuD′ to ClpXP for degradation, thereby providing a mechanism whereby cells can limit error-prone DNA replication.

Documentos Relacionados

• Distinct peptide signals in the UmuD and UmuD′ subunits of UmuD/D′ mediate tethering and substrate processing by the ClpXP protease
• Effects of protein stability and structure on substrate processing by the ClpXP unfolding and degradation machine
• The Escherichia coli SOS mutagenesis proteins UmuD and UmuD′ interact physically with the replicative DNA polymerase
• Regulation of Escherichia coli starvation sigma factor (sigma s) by ClpXP protease.
• The RssB response regulator directly targets σS for degradation by ClpXP