AI Article Synopsis
- Interaction mapping is a technique used to understand the role of proteins and their interactions, particularly focusing on the human AAA+ ATPase p97 and its link to 14 proteins.
- The study found that the protein ASPL promotes the disassembly of p97 into stable complexes, which is crucial for understanding its function.
- The research suggests that manipulating ASPL could lead to therapeutic strategies, including anti-cancer treatments, by targeting p97’s activity in cellular processes.
Article Abstract
Interaction mapping is a powerful strategy to elucidate the biological function of protein assemblies and their regulators. Here, we report the generation of a quantitative interaction network, directly linking 14 human proteins to the AAA+ ATPase p97, an essential hexameric protein with multiple cellular functions. We show that the high-affinity interacting protein ASPL efficiently promotes p97 hexamer disassembly, resulting in the formation of stable p97:ASPL heterotetramers. High-resolution structural and biochemical studies indicate that an extended UBX domain (eUBX) in ASPL is critical for p97 hexamer disassembly and facilitates the assembly of p97:ASPL heterotetramers. This spontaneous process is accompanied by a reorientation of the D2 ATPase domain in p97 and a loss of its activity. Finally, we demonstrate that overproduction of ASPL disrupts p97 hexamer function in ERAD and that engineered eUBX polypeptides can induce cell death, providing a rationale for developing anti-cancer polypeptide inhibitors that may target p97 activity.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5080433 | PMC |
| http://dx.doi.org/10.1038/ncomms13047 | DOI Listing |
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