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Molecular Mechanism of Processing Ubiquitinated Substrates by p97 and Its Main Cofactors

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p97(also known as Cdc48 or VCP) is a conserved AAA+ ATPase that plays a key role in diverse cellular pathways and processes. p97 segregates damaged or misfolded substrates from cellular organelles or membranes in corporation with its cofactors. These cofactors regulate p97’s function by its directing to different cellular pathways and have diverse effect on p97´s conformation. Recently, several high-resolution structures of substrate-engaged p97 in complex with cofactors have been resolved, providing structural insights into the molecular mechanism of substrate processing. In this review, we present a comprehensive overview of how p97 in complex with substrate recruiting and substrate processing cofactors recognize, extract, translocate, unfold and release ubiquitinated substrates.
Title: Molecular Mechanism of Processing Ubiquitinated Substrates by p97 and Its Main Cofactors
Description:
p97(also known as Cdc48 or VCP) is a conserved AAA+ ATPase that plays a key role in diverse cellular pathways and processes.
p97 segregates damaged or misfolded substrates from cellular organelles or membranes in corporation with its cofactors.
These cofactors regulate p97’s function by its directing to different cellular pathways and have diverse effect on p97´s conformation.
Recently, several high-resolution structures of substrate-engaged p97 in complex with cofactors have been resolved, providing structural insights into the molecular mechanism of substrate processing.
In this review, we present a comprehensive overview of how p97 in complex with substrate recruiting and substrate processing cofactors recognize, extract, translocate, unfold and release ubiquitinated substrates.

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