Molecular mechanism of substrate processing by the Cdc48 ATPase complex
| Autor: | Tom A. Rapoport, Nicholas O. Bodnar |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Models Molecular Saccharomyces cerevisiae Proteins ATPase Cell Cycle Proteins Saccharomyces cerevisiae Ring (chemistry) General Biochemistry Genetics and Molecular Biology Cofactor Article Deubiquitinating enzyme 03 medical and health sciences ATP hydrolysis Valosin Containing Protein Endopeptidases Animals Amino Acid Sequence Adenosine Triphosphatases biology Ubiquitin ATPase complex Substrate (chemistry) 030104 developmental biology Membrane Biochemistry biology.protein Biophysics |
| Popis: | The Cdc48 ATPase and its cofactors Ufd1/Npl4 (UN) extract polyubiquitinated proteins from membranes or macromolecular complexes, but how they perform these functions is unclear. Cdc48 consists of an N-terminal domain that binds UN and two stacked hexameric ATPase rings (D1 and D2) surrounding a central pore. Here, we use purified components to elucidate how the Cdc48 complex processes substrates. After interaction of the polyubiquitin chain with UN, ATP hydrolysis by the D2 ring moves the polypeptide completely through the double ring, generating a pulling force on the substrate and causing its unfolding. ATP hydrolysis by the D1 ring is important for subsequent substrate release from the Cdc48 complex. This release requires cooperation of Cdc48 with a deubiquitinase, which trims polyubiquitin to an oligoubiquitin chain that is then also translocated through the pore. Together, these results lead to a new paradigm for the function of Cdc48 and its mammalian ortholog p97/VCP. |
| Databáze: | OpenAIRE |
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