Two major stable structures of amyloid-forming peptides: amorphous aggregates and amyloid fibrils

Nishikawa, Naohiro; Sakae, Yoshitake; Gouda, Takuya; Tsujimura, Yuichiro; Okamoto, Yuko

doi:10.1080/08927022.2017.1359746

Cited by 6 publications

(2 citation statements)

References 45 publications

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“…Furthermore, protein condensates, which are initially liquidlike could acquire solid-like characteristics as they age, which is manifested by an increase in the relaxation time as the waiting time of the experiment increases (23). These observations suggest that the diagram of states as well as the dynamics of IDPs are complex and are determined by the various environmental factors (for example, pH change can induce a transition between fibrils and amorphous aggregates (24)(25)(26)).…”

Section: R a F Tmentioning

confidence: 99%

Sequence Complexity and Monomer Rigidity Control the Morphologies and Aging Dynamics of Protein Aggregates

Takaki,

Thirumalai

2024

Preprint

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Understanding the biophysical basis of protein aggregation is important in biology because of the potential link to several misfolding diseases. Although experiments have shown that protein aggregates adopt a variety of morphologies, the dynamics of their formation are less well characterized. Here, we introduce a minimal model to explore the dependence of the aggregation dynamics on the structural and sequence features of the monomers. Using simulations we demonstrate that sequence complexity (codified in terms of word entropy) and monomer rigidity profoundly influence the dynamics and morphology of the aggregates. Flexible monomers with low sequence complexity (corresponding to repeat sequences) form liquid-like droplets that exhibit ergodic behavior. Strikingly, these aggregates abruptly transition to more ordered structures, reminiscent of amyloid fibrils, when the monomer rigidity is increased. In contrast, aggregates resulting from monomers with high sequence complexity are amorphous and display non-ergodic glassy dynamics. The heterogeneous dynamics of the low and high-complexity sequences follow stretched exponential kinetics, which is one of the characteristics of glassy dynamics. Importantly, at non-zero values of the bending rigidities, the aggregates age with the relaxation times that increase with the waiting time. Informed by these findings, we provide insights into aging dynamics in protein condensates and contrast the behavior with the dynamics expected in RNA repeat sequences. Our findings underscore the influence of the monomer characteristics in shaping the morphology and dynamics of protein aggregates, thus providing a foundation for deciphering the general rules governing the behavior of protein condensates.Significance StatementProtein aggregates exhibit diverse morphology, exemplified by amyloid fibrils, gel-like structures, and liquid-like condensates. Differences in the morphologies in identical proteins play important functional roles in several diseases. Simulations using a minimal model show that such structures are encoded in the sequence complexity and bending rigidity of the monomers. The low-complexity flexible sequences form liquid droplets, whose relaxation dynamics are ergodic. In contrast, rigid low and high-complexity sequences, which form ordered nematic fibril-like structures and amorphous aggregates, exhibit heterogenous, non-ergodic dynamics. The relaxation times under these conditions increase as the waiting time increases, which is a signature of aging. The implications of our findings for aging in intrinsically dis-ordered proteins and repeat RNA sequences are outlined.

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Section: R a F Tmentioning

confidence: 99%

Sequence Complexity and Monomer Rigidity Control the Morphologies and Aging Dynamics of Protein Aggregates

Takaki,

Thirumalai

2024

Preprint

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“…Amyloid aggregates are divided into two classes: Amyloid fibrils of ordered structures and amorphous aggregates [ 13 , 14 , 15 , 16 ]. Amyloids have a number of specific characteristics, such as an ability to bind the dyes Congo Red and Thioflavin T (ThT); they are insoluble in most solvents and are stable to proteases [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Amyloid Aggregates of Smooth-Muscle Titin Impair Cell Adhesion

Bobylev

Фадеев

Bobyleva

et al. 2021

IJMS

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Various amyloid aggregates, in particular, aggregates of amyloid β-proteins, demonstrate in vitro and in vivo cytotoxic effects associated with impairment of cell adhesion. We investigated the effect of amyloid aggregates of smooth-muscle titin on smooth-muscle-cell cultures. The aggregates were shown to impair cell adhesion, which was accompanied by disorganization of the actin cytoskeleton, formation of filopodia, lamellipodia, and stress fibers. Cells died after a 72-h contact with the amyloid aggregates. To understand the causes of impairment, we studied the effect of the microtopology of a titin-amyloid-aggregate-coated surface on fibroblast adhesion by atomic force microscopy. The calculated surface roughness values varied from 2.7 to 4.9 nm, which can be a cause of highly antiadhesive properties of this surface. As all amyloids have the similar structure and properties, it is quite likely that the antiadhesive effect is also intrinsic to amyloid aggregates of other proteins. These results are important for understanding the mechanisms of the negative effect of amyloids on cell adhesion.

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Amyloids, amorphous aggregates and assemblies of peptides – Assessing aggregation

Juković,

Ratkaj,

Kalafatovic

et al. 2024

Biophysical Chemistry

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Two major stable structures of amyloid-forming peptides: amorphous aggregates and amyloid fibrils

Cited by 6 publications

References 45 publications

Sequence Complexity and Monomer Rigidity Control the Morphologies and Aging Dynamics of Protein Aggregates

Sequence Complexity and Monomer Rigidity Control the Morphologies and Aging Dynamics of Protein Aggregates

Amyloid Aggregates of Smooth-Muscle Titin Impair Cell Adhesion

Amyloids, amorphous aggregates and assemblies of peptides – Assessing aggregation

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