Ubiquitin Interacting Motifs: Duality Between Structured and Disordered Motifs
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Ubiquitin Interacting Motifs : Duality Between Structured and Disordered Motifs. / Lambrughi, Matteo; Maiani, Emiliano; Fas, Burcu Aykac; Shaw, Gary S.; Kragelund, Birthe B.; Lindorff-Larsen, Kresten; Teilum, Kaare; Invernizzi, Gaetano; Papaleo, Elena.
In: Frontiers in Molecular Biosciences, Vol. 8, 676235, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Ubiquitin Interacting Motifs
T2 - Duality Between Structured and Disordered Motifs
AU - Lambrughi, Matteo
AU - Maiani, Emiliano
AU - Fas, Burcu Aykac
AU - Shaw, Gary S.
AU - Kragelund, Birthe B.
AU - Lindorff-Larsen, Kresten
AU - Teilum, Kaare
AU - Invernizzi, Gaetano
AU - Papaleo, Elena
PY - 2021
Y1 - 2021
N2 - Ubiquitin is a small protein at the heart of many cellular processes, and several different protein domains are known to recognize and bind ubiquitin. A common motif for interaction with ubiquitin is the Ubiquitin Interacting Motif (UIM), characterized by a conserved sequence signature and often found in multi-domain proteins. Multi-domain proteins with intrinsically disordered regions mediate interactions with multiple partners, orchestrating diverse pathways. Short linear motifs for binding are often embedded in these disordered regions and play crucial roles in modulating protein function. In this work, we investigated the structural propensities of UIMs using molecular dynamics simulations and NMR chemical shifts. Despite the structural portrait depicted by X-crystallography of stable helical structures, we show that UIMs feature both helical and intrinsically disordered conformations. Our results shed light on a new class of disordered UIMs. This group is here exemplified by the C-terminal domain of one isoform of ataxin-3 and a group of ubiquitin-specific proteases. Intriguingly, UIMs not only bind ubiquitin. They can be a recruitment point for other interactors, such as parkin and the heat shock protein Hsc70-4. Disordered UIMs can provide versatility and new functions to the client proteins, opening new directions for research on their interactome.
AB - Ubiquitin is a small protein at the heart of many cellular processes, and several different protein domains are known to recognize and bind ubiquitin. A common motif for interaction with ubiquitin is the Ubiquitin Interacting Motif (UIM), characterized by a conserved sequence signature and often found in multi-domain proteins. Multi-domain proteins with intrinsically disordered regions mediate interactions with multiple partners, orchestrating diverse pathways. Short linear motifs for binding are often embedded in these disordered regions and play crucial roles in modulating protein function. In this work, we investigated the structural propensities of UIMs using molecular dynamics simulations and NMR chemical shifts. Despite the structural portrait depicted by X-crystallography of stable helical structures, we show that UIMs feature both helical and intrinsically disordered conformations. Our results shed light on a new class of disordered UIMs. This group is here exemplified by the C-terminal domain of one isoform of ataxin-3 and a group of ubiquitin-specific proteases. Intriguingly, UIMs not only bind ubiquitin. They can be a recruitment point for other interactors, such as parkin and the heat shock protein Hsc70-4. Disordered UIMs can provide versatility and new functions to the client proteins, opening new directions for research on their interactome.
KW - intrinsic disorder
KW - molecular dynamics
KW - moonlight functions
KW - peptide arrays
KW - short linear motifs
KW - ubiquitin
U2 - 10.3389/fmolb.2021.676235
DO - 10.3389/fmolb.2021.676235
M3 - Journal article
C2 - 34262938
AN - SCOPUS:85109710433
VL - 8
JO - Frontiers in Molecular Biosciences
JF - Frontiers in Molecular Biosciences
SN - 2296-889X
M1 - 676235
ER -
ID: 275887496