Panel of Engineered Ubiquitin Variants Targeting the Family of Human Ubiquitin Interacting Motifs.

ABSTRACT: Ubiquitin (Ub)-binding domains embedded in intracellular proteins act as readers of the complex Ub code and contribute to regulation of numerous eukaryotic processes. Ub-interacting motifs (UIMs) are short α-helical modular recognition elements whose role in controlling proteostasis and signal transduction has been poorly investigated. Moreover, impaired or aberrant activity of UIM-containing proteins has been implicated in numerous diseases, but targeting modular recognition elements in proteins remains a major challenge. To overcome this limitation, we developed Ub variants (UbVs) that bind to 42 UIMs in the human proteome with high affinity and specificity. Structural analysis of a UbV:UIM complex revealed the molecular determinants of enhanced affinity and specificity. Furthermore, we

SUBMITTER: Veggiani G 

PROVIDER: S-EPMC9305627 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature