When ribosomes pick the structure

Sivertsson, Elin M.; Itzhaki, Laura S.

doi:10.1038/nchem.1926

Cited by 3 publications

(3 citation statements)

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“…Protein engineering analysis of p16, myotrophin and gankyrin mapped out their kinetic folding and unfolding pathways and revealed polarized transition states in which structure was localized to a subset of repeats at one end of the protein [21][22][23][24][25], whereas in Notch the central repeats were structured in the transition state [26]. It was shown that the order in which the repeats fold is governed by their relative stabilities, with the most stable repeats folding first, and consequently, the folding pathways can be redirected relatively straightforwardly by manipulating the stability distribution across the repeat array [23,[25][26][27]. It follows also that under any given set of conditions there may be flux through multiple alternative pathways [23], as originally predicted by Wolynes and co-workers [28].…”

Section: Cooperativity In the Folding Of Tandem-repeat Proteins: Relationship To Function?mentioning

confidence: 99%

Folding cooperativity and allosteric function in the tandem-repeat protein class

Perez-Riba¹,

Synakewicz²,

Itzhaki³

2018

Phil. Trans. R. Soc. B

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The term allostery was originally developed to describe structural changes in one binding site induced by the interaction of a partner molecule with a distant binding site, and it has been studied in depth in the field of enzymology. Here, we discuss the concept of action at a distance in relation to the folding and function of the solenoid class of tandem-repeat proteins such as tetratricopeptide repeats (TPRs) and ankyrin repeats. Distantly located repeats fold cooperatively, even though only nearest-neighbour interactions exist in these proteins. A number of repeat-protein scaffolds have been reported to display allosteric effects, transferred through the repeat array, that enable them to direct the activity of the multi-subunit enzymes within which they reside. We also highlight a recently identified group of tandem-repeat proteins, the RRPNN subclass of TPRs, recent crystal structures of which indicate that they function as allosteric switches to modulate multiple bacterial quorum-sensing mechanisms. We believe that the folding cooperativity of tandem-repeat proteins and the biophysical mechanisms that transform them into allosteric switches are intimately intertwined. This opinion piece aims to combine our understanding of the two areas and develop ideas on their common underlying principles.This article is part of a discussion meeting issue 'Allostery and molecular machines'.

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Section: Cooperativity In the Folding Of Tandem-repeat Proteins: Relationship To Function?mentioning

confidence: 99%

Folding cooperativity and allosteric function in the tandem-repeat protein class

Perez-Riba¹,

Synakewicz²,

Itzhaki³

2018

Phil. Trans. R. Soc. B

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“…The most well-known example in this context is probably the case of ribonuclease folding, enunciated by the 1972 Nobel Laureate in Chemistry-Christian B. Anfinsen-in the principle now known as the Anfinsen's dogma. Anfinsen, in his studies of ribonuclease folding, had postulated that a primary protein sequence could be used to predict the final folded structure of a protein uniquely, given that the native state minima in the potential energy surface (PES) is unchallenged by any other comparative structure of the protein, and the path leading from unfolded to folded state is kinetically and thermodynamically accessible without having to go through complex conformational requirements [183,184]. It is interesting to note that amyloids-our current topic of interest-are an exception to this dogma as they represent an additional minimum other than that of the native state of the protein in the folding funnel.…”

Section: Protein Aggregation and Its Mechanismsmentioning

confidence: 99%

“…The native monomer similarly can either undergo partial unfolding and/or associate with the forming nucleus [181,183,184]. When the concentration of amyloid fibrils increases significantly, the secondary processes take over as the dominant phenomenon [185].…”

Section: Kinetics and Mechanisms Of Amyloid Formationmentioning

confidence: 99%

Amyloidogenesis: What Do We Know So Far?

Alraawi

Banerjee

Mohanty

et al. 2022

IJMS

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The study of protein aggregation, and amyloidosis in particular, has gained considerable interest in recent times. Several neurodegenerative diseases, such as Alzheimer’s (AD) and Parkinson’s (PD) show a characteristic buildup of proteinaceous aggregates in several organs, especially the brain. Despite the enormous upsurge in research articles in this arena, it would not be incorrect to say that we still lack a crystal-clear idea surrounding these notorious aggregates. In this review, we attempt to present a holistic picture on protein aggregation and amyloids in particular. Using a chronological order of discoveries, we present the case of amyloids right from the onset of their discovery, various biophysical techniques, including analysis of the structure, the mechanisms and kinetics of the formation of amyloids. We have discussed important questions on whether aggregation and amyloidosis are restricted to a subset of specific proteins or more broadly influenced by the biophysiochemical and cellular environment. The therapeutic strategies and the significant failure rate of drugs in clinical trials pertaining to these neurodegenerative diseases have been also discussed at length. At a time when the COVID-19 pandemic has hit the globe hard, the review also discusses the plausibility of the far-reaching consequences posed by the virus, such as triggering early onset of amyloidosis. Finally, the application(s) of amyloids as useful biomaterials has also been discussed briefly in this review.

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