scholarly journals Molecular Recognition by Templated Folding of an Intrinsically Disordered Protein

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Angelo Toto ◽  
Carlo Camilloni ◽  
Rajanish Giri ◽  
Maurizio Brunori ◽  
Michele Vendruscolo ◽  
...  
Keyword(s):  
Molecular Recognition ◽  
Intrinsically Disordered Protein ◽  
Intrinsically Disordered ◽  
Disordered Protein

scholarly journals A molecular recognition feature mediates ribosome-induced SRP-receptor assembly during protein targeting

2019 ◽  
Vol 218 (10) ◽  
pp. 3307-3319 ◽  
Author(s):  
Yu-Hsien Hwang Fu ◽  
Sowmya Chandrasekar ◽  
Jae Ho Lee ◽  
Shu-ou Shan
Keyword(s):  
Molecular Recognition ◽  
Protein Targeting ◽  
Signal Recognition Particle ◽  
Intrinsically Disordered Protein ◽  
Signal Recognition ◽  
Cellular Functions ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Linker Domain ◽  
Receptor Assembly

Molecular recognition features (MoRFs) provide interaction motifs in intrinsically disordered protein regions to mediate diverse cellular functions. Here we report that a MoRF element, located in the disordered linker domain of the mammalian signal recognition particle (SRP) receptor and conserved among eukaryotes, plays an essential role in sensing the ribosome during cotranslational protein targeting to the endoplasmic reticulum. Loss of the MoRF in the SRP receptor (SR) largely abolishes the ability of the ribosome to activate SRP-SR assembly and impairs cotranslational protein targeting. These results demonstrate a novel role for MoRF elements and provide a mechanism for the ribosome-induced activation of the mammalian SRP pathway. Kinetic analyses and comparison with the bacterial SRP further suggest that the SR MoRF functionally replaces the essential GNRA tetraloop in the bacterial SRP RNA, providing an example for the replacement of RNA function by proteins during the evolution of ancient ribonucleoprotein particles.

scholarly journals Molecular recognition features (MoRFs) in three domains of life

2016 ◽  
Vol 12 (3) ◽  
pp. 697-710 ◽  
Author(s):  
Jing Yan ◽  
A. Keith Dunker ◽  
Vladimir N. Uversky ◽  
Lukasz Kurgan
Keyword(s):  
Amino Acid ◽  
Molecular Recognition ◽  
Protein Binding ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Intrinsically Disordered Protein ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Domains Of Life ◽  
Molecular Recognition Features

MoRFs are widespread intrinsically disordered protein-binding regions that have similar abundance and amino acid composition across the three domains of life.

Self-Assembling Micelles Based on an Intrinsically Disordered Protein Domain

2018 ◽  
Author(s):  
Sarah Klass ◽  
Matthew J. Smith ◽  
Tahoe Fiala ◽  
Jessica Lee ◽  
Anthony Omole ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Fusion Proteins ◽  
Organic Molecules ◽  
Intrinsically Disordered Protein ◽  
Protein Domain ◽  
Enzymatic Cleavage ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Self Assembling ◽  
Protein Tag

Herein, we describe a new series of fusion proteins that have been developed to self-assemble spontaneously into stable micelles that are 27 nm in diameter after enzymatic cleavage of a solubilizing protein tag. The sequences of the proteins are based on a human intrinsically disordered protein, which has been appended with a hydrophobic segment. The micelles were found to form across a broad range of pH, ionic strength, and temperature conditions, with critical micelle concentration (CMC) values below 1 µM being observed in some cases. The reported micelles were found to solubilize hydrophobic metal complexes and organic molecules, suggesting their potential suitability for catalysis and drug delivery applications.

scholarly journals Mutations of Intrinsically Disordered Protein Regions Can Drive Cancer but Lack Therapeutic Strategies

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 381
Author(s):  
Bálint Mészáros ◽  
Borbála Hajdu-Soltész ◽  
András Zeke ◽  
Zsuzsanna Dosztányi
Keyword(s):  
Gene Expression Regulation ◽  
Treatment Options ◽  
Intrinsically Disordered Protein ◽  
System Level ◽  
Alternative Mechanism ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Disordered Protein ◽  
Cancer Types ◽  
Cancer Drivers

Many proteins contain intrinsically disordered regions (IDRs) which carry out important functions without relying on a single well-defined conformation. IDRs are increasingly recognized as critical elements of regulatory networks and have been also associated with cancer. However, it is unknown whether mutations targeting IDRs represent a distinct class of driver events associated with specific molecular and system-level properties, cancer types and treatment options. Here, we used an integrative computational approach to explore the direct role of intrinsically disordered protein regions driving cancer. We showed that around 20% of cancer drivers are primarily targeted through a disordered region. These IDRs can function in multiple ways which are distinct from the functional mechanisms of ordered drivers. Disordered drivers play a central role in context-dependent interaction networks and are enriched in specific biological processes such as transcription, gene expression regulation and protein degradation. Furthermore, their modulation represents an alternative mechanism for the emergence of all known cancer hallmarks. Importantly, in certain cancer patients, mutations of disordered drivers represent key driving events. However, treatment options for such patients are currently severely limited. The presented study highlights a largely overlooked class of cancer drivers associated with specific cancer types that need novel therapeutic options.

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