Site-specific ubiquitination affects protein energetics and proteasomal degradation.

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 Biol

journal_title

Nature chemical biology

authors

Carroll EC,Greene ER,Martin A,Marqusee S

doi

10.1038/s41589-020-0556-3

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

866-875

issue

8

eissn

1552-4450

issn

1552-4469

pii

10.1038/s41589-020-0556-3

journal_volume

16

pub_type

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