The Transcriptional Repressor RYBP Is a Natively Unfolded Protein Which Folds upon Binding to DNA†

Biochemistry ◽  
2009 ◽  
Vol 48 (6) ◽  
pp. 1348-1360 ◽  
Author(s):  
José L. Neira ◽  
Mónica Román-Trufero ◽  
Lellys M. Contreras ◽  
Jesús Prieto ◽  
Gagandeep Singh ◽  
...  
Keyword(s):  
Transcriptional Repressor ◽  
Unfolded Protein ◽  
Natively Unfolded Protein ◽  
Natively Unfolded

scholarly journals Human full-length Securin is a natively unfolded protein

2009 ◽  
Vol 14 (6) ◽  
pp. 1410-1418 ◽  
Author(s):  
Nuria Sánchez-Puig ◽  
Dmitry B. Veprintsev ◽  
Alan R. Fersht
Keyword(s):  
Full Length ◽  
Unfolded Protein ◽  
Natively Unfolded Protein ◽  
Natively Unfolded

scholarly journals The interplay between lipids and dopamine on α-synuclein oligomerization and membrane binding

2013 ◽  
Vol 33 (5) ◽  
Author(s):  
Chi L. L. Pham ◽  
Roberto Cappai
Keyword(s):  
Lipid Membranes ◽  
Amyloid Fibrils ◽  
Lipid Membrane ◽  
Hydrophobic Interactions ◽  
Membrane Integrity ◽  
Lipid Vesicles ◽  
Helical Conformation ◽  
Unfolded Protein ◽  
Natively Unfolded Protein ◽  
Natively Unfolded

The deposition of α-syn (α-synuclein) as amyloid fibrils and the selective loss of DA (dopamine) containing neurons in the substantia nigra are two key features of PD (Parkinson's disease). α-syn is a natively unfolded protein and adopts an α-helical conformation upon binding to lipid membrane. Oligomeric species of α-syn have been proposed to be the pathogenic species associated with PD because they can bind lipid membranes and disrupt membrane integrity. DA is readily oxidized to generate reactive intermediates and ROS (reactive oxygen species) and in the presence of DA, α-syn form of SDS-resistant soluble oligomers. It is postulated that the formation of the α-syn:DA oligomers involves the cross-linking of DA-melanin with α-syn, via covalent linkage, hydrogen and hydrophobic interactions. We investigate the effect of lipids on DA-induced α-syn oligomerization and studied the ability of α-syn:DA oligomers to interact with lipids vesicles. Our results show that the interaction of α-syn with lipids inhibits the formation of DA-induced α-syn oligomers. Moreover, the α-syn:DA oligomer cannot interact with lipid vesicles or cause membrane permeability. Thus, the formation of α-syn:DA oligomers may alter the actions of α-syn which require membrane association, leading to disruption of its normal cellular function.

scholarly journals The Properties of α-Synuclein Secondary Nuclei are Dominated by the Solution Conditions Rather than the Seed Fibril Strain

2019 ◽  
Author(s):  
Alessia Peduzzo ◽  
Sara Linse ◽  
Alexander Buell
Keyword(s):  
Amyloid Fibrils ◽  
Lewy Bodies ◽  
The Other ◽  
Secondary Nucleation ◽  
Presynaptic Terminals ◽  
Unfolded Protein ◽  
Primary Nucleation ◽  
Other Hand ◽  
Natively Unfolded Protein ◽  
Natively Unfolded

α-synuclein (α-syn) is a natively unfolded protein predominantly localized in the presynaptic terminals of neurons. It has been shown that α-syn fibrils are the major component of abnormal neuronal aggregates known as Lewy bodies, the characteristic hallmark of Parkinson’s disease. Amyloid fibrils arise through primary nucleation from monomers, which in the case of α-syn is accelerated by suitable surfaces with an affinity for the protein, followed by the elongation of the nuclei by monomer addition. Secondary nucleation, on the other hand, corresponds to the formation of new fibrils when it is facilitated by pre-existing fibrils. While<br>α-synuclein (α-syn) is a natively unfolded protein predominantly localized in the presynaptic terminals of neurons. It has been shown that α-syn fibrils are the major component of abnormal neuronal aggregates known as Lewy bodies, the characteristic hallmark of Parkinson’s disease. Amyloid fibrils arise through primary nucleation from monomers, which in the case of α-syn is accelerated by suitable surfaces with an affinity for the protein, followed by the elongation of the nuclei by monomer addition. Secondary nucleation, on the other hand, corresponds to the formation of new fibrils when it is facilitated by pre-existing fibrils. While it is well-established that the newly added monomer in the process of fibril elongation adopts the conformation of the monomers in the seed, often called templating, it is still unclear under which conditions fibrils formed through secondary nucleation of monomers on the surface of fibrils copy the structure of the parent. Here we show by biochemical and microscopical methods that the secondary nucleation of α-syn, enabled at mildly acidic pH, leads to fibrils that structurally resemble more closely those formed de novo under the same conditions, rather than the seeds if these are formed under different solution condition. This result has important implications for the mechanistic understanding of the secondary nucleation of amyloid fibrils and its role in the propagation of aggregate pathology in protein misfolding diseases.<br>

scholarly journals SAXS Study of the PIR Domain from the Grb14 Molecular Adaptor: A Natively Unfolded Protein with a Transient Structure Primer?

2004 ◽  
Vol 87 (6) ◽  
pp. 4056-4064 ◽  
Author(s):  
K. Moncoq ◽  
I. Broutin ◽  
C.T. Craescu ◽  
P. Vachette ◽  
A. Ducruix ◽  
...  
Keyword(s):  
Unfolded Protein ◽  
Natively Unfolded Protein ◽  
Natively Unfolded ◽  
Transient Structure
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