scholarly journals Zinc induced structural changes in the intrinsically disordered BDNF Met prodomain confer synaptic elimination

Metallomics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 1208-1219 ◽  
Author(s):  
Jing Wang ◽  
Agustin Anastasia ◽  
Henrietta Bains ◽  
Joanna I. Giza ◽  
David G. Clossey ◽  
...  
Keyword(s):  
Human Brain ◽  
Neurotrophic Factor ◽  
Structural Changes ◽  
Intrinsically Disordered Protein ◽  
Brain Derived Neurotrophic Factor ◽  
Protein Product ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Mature Domain

Human brain derived neurotrophic factor (BDNF) encodes a protein product consisting of a C-terminal mature domain (mature BDNF) and an N-terminal prodomain, which is an intrinsically disordered protein.

Monitoring structural changes in intrinsically disordered proteins using QCM-D: application to the bacterial cell division protein ZipA

2016 ◽  
Vol 52 (39) ◽  
pp. 6541-6544 ◽  
Author(s):  
Pablo Mateos-Gil ◽  
Achilleas Tsortos ◽  
Marisela Vélez ◽  
Electra Gizeli
Keyword(s):  
Cell Division ◽  
Structural Changes ◽  
Intrinsically Disordered Proteins ◽  
Intrinsically Disordered Protein ◽  
Disordered Proteins ◽  
Bacterial Cell Division ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Cell Division Protein

Characterization of structural changes in an intrinsically disordered protein attached on a QCM-D, with a sensitivity of 1.8 nm or better.

scholarly journals The Non-Fibrillating N-Terminal of α-Synuclein Binds and Co-Fibrillates with Heparin

Biomolecules ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1192
Author(s):  
Line K. Skaanning ◽  
Angelo Santoro ◽  
Thomas Skamris ◽  
Jacob Hertz Martinsen ◽  
Anna Maria D’Ursi ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Structural Changes ◽  
Lewy Bodies ◽  
Intrinsically Disordered Protein ◽  
Molar Ratio ◽  
Type I ◽  
Dependent Manner ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Main Component

The intrinsically disordered protein α-synuclein (aSN) is, in its fibrillated state, the main component of Lewy bodies—hallmarks of Parkinson’s disease. Additional Lewy body components include glycosaminoglycans, including heparan sulfate proteoglycans. In humans, heparan sulfate has, in an age-dependent manner, shown increased levels of sulfation. Heparin, a highly sulfated glycosaminoglycan, is a relevant mimic for mature heparan sulfate and has been shown to influence aSN fibrillation. Here, we decompose the underlying properties of the interaction between heparin and aSN and the effect of heparin on fibrillation. Via the isolation of the first 61 residues of aSN, which lacked intrinsic fibrillation propensity, fibrillation could be induced by heparin, and access to the initial steps in fibrillation was possible. Here, structural changes with shifts from disorder via type I β-turns to β-sheets were revealed, correlating with an increase in the aSN1–61/heparin molar ratio. Fluorescence microscopy revealed that heparin and aSN1–61 co-exist in the final fibrils. We conclude that heparin can induce the fibrillation of aSN1–61, through binding to the N-terminal with an affinity that is higher in the truncated form of aSN. It does so by specifically modulating the structure of aSN via the formation of type I β-turn structures likely critical for triggering aSN fibrillation.

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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