Mechanisms and Consequences of Protein Aggregation: The Role of Folding Intermediates

AbstractDisulfide-containing proteins are ideal models for studies of protein folding as the folding intermediates can be observed, trapped, and separated by HPLC during the folding reaction. However, regulating or analyzing the structures of folding intermediates of peptides and proteins continues to be a difficult problem. Recently, the development of several techniques in peptide chemistry and biotechnology has resulted in the availability of some powerful tools for studying protein folding in the context of the structural analysis of native, mutant proteins, and folding intermediates. In this review, recent developments in the field of disulfide-coupled peptide and protein folding are discussed, from the viewpoint of chemical and biotechnological methods, such as analytical methods for the detection of disulfide pairings, chemical methods for disulfide bond formation between the defined Cys residues, and applications of diselenide bonds for the regulation of disulfide-coupled peptide and protein folding.

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An in vitro study of the role of docosahexaenoic acid in human tau protein aggregation

Journal of Biomolecular Structure and Dynamics ◽

10.1080/07391102.2016.1248489 ◽

2016 ◽

Vol 35 (14) ◽

pp. 3176-3181

Author(s):

Elham Sadat Mostafavi ◽

Mohammad Ali Nasiri Khalili ◽

Sirus Khodadadi ◽

Gholam Hossein Riazi

Keyword(s):

Docosahexaenoic Acid ◽

Protein Aggregation ◽

Tau Protein ◽

In Vitro Study ◽

Vitro Study

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Partial Unfolding of a Monoclonal Antibody: Role of a Single Domain in Driving Protein Aggregation

Biochemistry ◽

10.1021/bi5002163 ◽

2014 ◽

Vol 53 (20) ◽

pp. 3367-3377 ◽

Cited By ~ 20

Author(s):

Shyam B. Mehta ◽

Jared S. Bee ◽

Theodore W. Randolph ◽

John F. Carpenter

Keyword(s):

Monoclonal Antibody ◽

Protein Aggregation ◽

Single Domain ◽

Partial Unfolding

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Protein aggregation inEscherichia coli: role of proteases

FEMS Microbiology Letters ◽

10.1111/j.1574-6968.2002.tb11020.x ◽

2002 ◽

Vol 207 (1) ◽

pp. 9-12 ◽

Cited By ~ 60

Author(s):

Ran Rosen ◽

Dvora Biran ◽

Eyal Gur ◽

DÃ¶rte Becher ◽

Michael Hecker ◽

...

Keyword(s):

Protein Aggregation ◽

Inescherichia Coli

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Role of (single/double chain surfactant) micelles on the protein aggregation

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2018.10.145 ◽

2019 ◽

Vol 122 ◽

pp. 72-81 ◽

Cited By ~ 10

Author(s):

Rachana Srivastava ◽

Md. Sayem Alam

Keyword(s):

Protein Aggregation ◽

Double Chain ◽

Surfactant Micelles

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Protein Aggregation/Folding: The Role of Deterministic Singularities of Sequence Hydrophobicity as Determined by Nonlinear Signal Analysis of Acylphosphatase and Aβ(1–40)

Biophysical Journal ◽

10.1016/s0006-3495(03)74774-2 ◽

2003 ◽

Vol 85 (6) ◽

pp. 3544-3557 ◽

Cited By ~ 31

Author(s):

Joseph P. Zbilut ◽

Alfredo Colosimo ◽

Filippo Conti ◽

Mauro Colafranceschi ◽

Cesare Manetti ◽

...

Keyword(s):

Protein Aggregation ◽

Signal Analysis ◽

Nonlinear Signal ◽

Nonlinear Signal Analysis

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Prions: Protein Aggregation and Infectious Diseases

Physiological Reviews ◽

10.1152/physrev.00006.2009 ◽

2009 ◽

Vol 89 (4) ◽

pp. 1105-1152 ◽

Cited By ~ 316

Author(s):

Adriano Aguzzi ◽

Anna Maria Calella

Keyword(s):

Protein Aggregation ◽

Prion Diseases ◽

Physiological Role ◽

Infectious Agent ◽

Normal Function ◽

Cellular Prion Protein ◽

Transmissible Spongiform Encephalopathies ◽

Pathological Features ◽

Spongiform Encephalopathies

Transmissible spongiform encephalopathies (TSEs) are inevitably lethal neurodegenerative diseases that affect humans and a large variety of animals. The infectious agent responsible for TSEs is the prion, an abnormally folded and aggregated protein that propagates itself by imposing its conformation onto the cellular prion protein (PrPC) of the host. PrPCis necessary for prion replication and for prion-induced neurodegeneration, yet the proximal causes of neuronal injury and death are still poorly understood. Prion toxicity may arise from the interference with the normal function of PrPC, and therefore, understanding the physiological role of PrPCmay help to clarify the mechanism underlying prion diseases. Here we discuss the evolution of the prion concept and how prion-like mechanisms may apply to other protein aggregation diseases. We describe the clinical and the pathological features of the prion diseases in human and animals, the events occurring during neuroinvasion, and the possible scenarios underlying brain damage. Finally, we discuss potential antiprion therapies and current developments in the realm of prion diagnostics.

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