AI Article Synopsis

  • * IDRs allow proteins to take on multiple shapes, making it easier for them to interact with a wide range of other proteins, which is crucial for proteins that connect with many partners in cellular networks, like those involved in modifying proteins through ubiquitination.
  • * The yeast deubiquitinating enzyme Ubp10, which has IDRs around its active site, shows that these regions contain important binding modules that guide its interactions necessary for its roles in gene silencing and ribosome biogenesis, a concept also observed

Article Abstract

In the canonical view of protein function, it is generally accepted that the three-dimensional structure of a protein determines its function. However, the past decade has seen a dramatic growth in the identification of proteins with extensive intrinsically disordered regions (IDRs), which are conformationally plastic and do not appear to adopt single three-dimensional structures. One current paradigm for IDR function is that disorder enables IDRs to adopt multiple conformations, expanding the ability of a protein to interact with a wide variety of disparate proteins. The capacity for many interactions is an important feature of proteins that occupy the hubs of protein networks, in particular protein-modifying enzymes that usually have a broad spectrum of substrates. One such protein modification is ubiquitination, where ubiquitin is attached to proteins through ubiquitin ligases (E3s) and removed through deubiquitinating enzymes. Numerous proteomic studies have found that thousands of proteins are dynamically regulated by cycles of ubiquitination and deubiquitination. Thus, how these enzymes target their wide array of substrates is of considerable importance for understanding the function of the cell's diverse ubiquitination networks. Here, we characterize a yeast deubiquitinating enzyme, Ubp10, that possesses IDRs flanking its catalytic protease domain. We show that Ubp10 possesses multiple, distinct binding modules within its IDRs that are necessary and sufficient for directing protein interactions important for Ubp10's known roles in gene silencing and ribosome biogenesis. The human homolog of Ubp10, USP36, also has IDRs flanking its catalytic domain, and these IDRs similarly contain binding modules important for protein interactions. This work highlights the significant protein interaction scaffolding abilities of IDRs in the regulation of dynamic protein ubiquitination.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536463PMC
http://dx.doi.org/10.1074/jbc.M115.650952DOI Listing

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