Abstract:
:Changes in the cellular environment modulate protein energy landscapes to drive important biology, with consequences for signaling, allostery and other vital processes. The effects of ubiquitination are particularly important because of their potential influence on degradation by the 26S proteasome. Moreover, proteasomal engagement requires unstructured initiation regions that many known proteasome substrates lack. To assess the energetic effects of ubiquitination and how these manifest at the proteasome, we developed a generalizable strategy to produce isopeptide-linked ubiquitin within structured regions of a protein. The effects on the energy landscape vary from negligible to dramatic, depending on the protein and site of ubiquitination. Ubiquitination at sensitive sites destabilizes the native structure and increases the rate of proteasomal degradation. In well-folded proteins, ubiquitination can even induce the requisite unstructured regions needed for proteasomal engagement. Our results indicate a biophysical role of site-specific ubiquitination as a potential regulatory mechanism for energy-dependent substrate degradation.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Carroll EC,Greene ER,Martin A,Marqusee Sdoi
10.1038/s41589-020-0556-3subject
Has Abstractpub_date
2020-08-01 00:00:00pages
866-875issue
8eissn
1552-4450issn
1552-4469pii
10.1038/s41589-020-0556-3journal_volume
16pub_type
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