Ubiquitin Interacting Motifs: Duality Between Structured and Disordered Motifs

• DOI: 10.3389/fmolb.2021.676235
• Publication Date: 2021-06-28T04:42:17Z
• Authors: Matteo Lambrughi; Emiliano Maiani; Burcu Aykac Fas; Gary S. Shaw; Birthe B. Kragelund; Kresten Lindorff-...; Kaare Teilum; Gaetano Invernizzi; Elena Papaleo
• Keywords: Deubiquitinating enzyme; Intrinsically Disordered Proteins; Structural motif; WW domain; Ubiquitin-Protein Ligases; Interactome; Ubiquitins

Ubiquitin is a small protein at the heart of many cellular processes, and several different domains are known to recognize bind ubiquitin. A common motif for interaction with ubiquitin Interacting Motif (UIM), characterized by conserved sequence signature often found in multi-domain proteins. Multi-domain proteins intrinsically disordered regions mediate interactions multiple partners, orchestrating diverse pathways. Short linear motifs binding embedded these play crucial roles modulating function. In this work, we investigated structural propensities UIMs using molecular dynamics simulations NMR chemical shifts. Despite portrait depicted X-crystallography stable helical structures, show that feature both conformations. Our results shed light on new class UIMs. This group here exemplified C-terminal domain one isoform ataxin-3 ubiquitin-specific proteases. Intriguingly, not only They can be recruitment point other interactors, such as parkin heat shock Hsc70-4. Disordered provide versatility functions client proteins, opening directions research their interactome.