Effect of Dehydration on the Aggregation Kinetics of Two Amyloid Peptides

Mukherjee, Smita; Chowdhury, P. K.; Gai, Feng

doi:10.1021/jp809817s

Cited by 82 publications

(116 citation statements)

References 61 publications

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“…For Ala-rich peptides, on the other hand, there was a noticeable increase in β-sheet content with above 80% β-sheet content estimated for the dehydrated peptide solution (Table T1), which may not only reflect that Ala-rich peptides have a very high β-sheet content, but also a β-sheet enrichment upon desolvation, a common mechanism in Amyloid fibers. [45] While quantification of protein secondary structure by ATR-FTIR must be judged with caution, including for amyloid-like peptides [46] this semi-quantitative analysis nonetheless allows us to conclude that all peptides exhibit a high propensity for β-sheet formation, thereby supporting our CD data.…”

Section: Complementary Atr-ftir Studiessupporting

confidence: 68%

Modular peptides from the thermoplastic squid sucker ring teeth form amyloid-like cross-β supramolecular networks

et al. 2016

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. (2016). Modular peptides from the thermoplastic squid sucker ring teeth form amyloid-like cross-supramolecular networks. Acta Biomaterialia. https://doi.org/10.1016/j.actbio.2016.09.040Citing this paper Please note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections. General rightsCopyright and moral rights for the publications made accessible in the Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognize and abide by the legal requirements associated with these rights.•Users may download and print one copy of any publication from the Research Portal for the purpose of private study or research.•You may not further distribute the material or use it for any profit-making activity or commercial gain •You may freely distribute the URL identifying the publication in the Research Portal Take down policy If you believe that this document breaches copyright please contact librarypure@kcl.ac.uk providing details, and we will remove access to the work immediately and investigate your claim. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThe hard sucker ring teeth (SRT) from decapodiforme cephalopods, which are located inside the sucker cups lining the arms and tentacles of these squid species, have recently emerged as a unique model structure for biomimetic structural biopolymers. SRT are entirely composed of modular, block co-polymer-like proteins that self-assemble into a large supramolecular network. In order to unveil the molecular principles behind the SRT's self-assembly and robustness, we describe a combinatorial screening assay that maps the molecular-scale interactions between the most abundant modular peptide blocks of suckerin proteins. By selecting prominent interaction hotspots from this assay, we identified four peptides that exhibited the strongest homo-peptidic interactions, and conducted further in-depth biophysical characterizations complemented by molecular dynamic (MD) simulations to investigate the nature of these interactions. Circular Dichroism (CD) revealed conformations that transitioned from semi-extended poly-proline II (PII) towards β-sheet structure. The peptides s...

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Section: Complementary Atr-ftir Studiessupporting

confidence: 68%

Modular peptides from the thermoplastic squid sucker ring teeth form amyloid-like cross-β supramolecular networks

et al. 2016

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“…This study tests this hypothesis and provides architecture in which Zn 2þ shares two peptides in Aβ 42 . Second, dehydration is known to be important for amyloid formation (38), and zinc coordination decreases the solvation energy for tightly packed oligomers. These two findings explain why zinc can promote amyloid formation and its role in Aβ aggregation.…”

Section: Resultsmentioning

confidence: 99%

Zinc ions promote Alzheimer Aβ aggregation via population shift of polymorphic states

Miller

Ma²,

Nussinov³

2010

Proc. Natl. Acad. Sci. U.S.A.

283

288

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Although a key factor in Alzheimer's disease etiology is enrichment of Zn 2þ in aggregates, and there are data suggesting that zinc promotes aggregation, how Zn 2þ -Aβ coordination promotes aggregation is elusive. Here we probe the structures and mechanisms through which Zn 2þ can affect amyloidosis. By covalently linking fragments (that have experiment-based coordinates) we observed that, in oligomeric Zn 2þ -Aβ 42 , Zn 2þ can simultaneously coordinate intra-and intermolecularly, bridging two peptides. Zinc coordination significantly decreases the solvation energy for large Zn 2þ -Aβ 42 oligomers and thus enhances their aggregation tendency. Zn 2þ binding does not change the β-sheet association around the C-terminal hydrophobic region; however, it shifts the relative population of the preexisting amyloid polymorphic ensembles. As a result, although a parallel β-sheet arrangement is still preferred, antiparallel and other less structured assemblies are stabilized, also becoming major species. Overall, Zn 2þ coordination promotes Aβ 42 aggregation leading to less uniform structures. Our replica exchange molecular dynamics simulations further reproduced an experimental observation that the increasing Zn 2þ concentration could slow down the aggregation rate, even though the aggregation rates are still much higher than in Zn 2þ -free solution.conformational selection | energy landscape | metal ions | modeling amyloid assemblies | seed polymorphism A lzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia in millions of people worldwide (1). This disease accounts for the majority of clinical senile dementia associated with the formation of senile plaques (2, 3). The primary constituent of the plaques is the aggregated Aβ 40 ∕Aβ 42 peptides in the brain; therefore, factors that influence the aggregation are of high interest.In vivo studies reported that Zn 2þ , Cu þ2 , and Fe þ3 are markedly enriched in Aβ plaques (4, 5), suggesting that these ions may act as seeding factors. Oligomerization of the Aβ peptides can be rapidly induced in the presence of Zn 2þ ions under physiological conditions (4, 6, 7). Noy et al. (8) have followed Zn 2þ ionenhanced Aβ aggregation. Studies suggested that H6, H13, and H14 at the N-terminal domain of Aβ coordinate with Zn 2þ (9-26). Solution NMR of Zn 2þ -Aβ 1-16 showed that Zn 2þ is bound to these three histidines and E11 (18). A recent NMR study of Zn 2þ -Aβ 1-28 proposed that Zn 2þ binds to H6, E11, H14, and D1 of rat Aβ 1-28 and to H6, E11, H13, H14, and D1 of human Aβ 1-28 (22). In addition, X-ray absorption spectroscopy revealed that Zn 2þ coordinates with four histidines, H13 and H14 of two adjacent monomers (23). Experimental structural data for Aβ 40 ∕Aβ 42 oligomers complexed with Zn 2þ are unavailable.Although it is believed that reducing zinc-induced Aβ aggregation can decrease toxicity (27), it was also postulated that zinc can lower Aβ toxicity by selectively precipitating aggregation intermediates (28). Key questions on the...

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“…These observations show that dehydration, resulting in the formation of the dry zipper region (4) as the monomer locks into the fibril lattice, is a key event in the growth of the amyloid fibrils. We surmise that interactions involving water must play an important role in the rate of fibril growth (41,42).…”

Section: Two-stage Dehydration and The Locking Process Are Coincidentmentioning

confidence: 94%

“…The crystal structures of the fibrils of the heptapeptide 7 GNNQQNY 13 , from the yeast prion protein Sup35, and the hexapeptide 37 GGVVIA 42 , from the A␤ protein, belong to 2 different classes (4,5). In the ordered state, the surfaces of the 2 different ␤-strands interlock to form a steric zipper structure in which the side chains of each ␤-sheet face at the interface, interdigitate into one another.…”

Section: Methodsmentioning

confidence: 99%

Dynamics of locking of peptides onto growing amyloid fibrils

Reddy¹,

Straub

Thirumalai

2009

Proc. Natl. Acad. Sci. U.S.A.

119

147

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Sequence-dependent variations in the growth mechanism and stability of amyloid fibrils, which are implicated in a number of neurodegenerative diseases, are poorly understood. We have carried out extensive all-atom molecular dynamics simulations to monitor the structural changes that occur upon addition of random coil (RC) monomer fragments from the yeast prion Sup35 and A␤-peptide onto a preformed fibril. Using the atomic resolution structures of the microcrystals as the starting points, we show that the RC 3 ␤-strand transition for the Sup35 fragment occurs abruptly over a very narrow time interval, whereas the acquisition of strand content is less dramatic for the hydrophobic-rich A␤-peptide. Expulsion of water, resulting in the formation of a dry interface between 2 adjacent sheets of the Sup35 fibril, occurs in 2 stages. Ejection of a small number of discrete water molecules in the second stage follows a rapid decrease in the number of water molecules in the first stage. Stability of the Sup35 fibril is increased by a network of hydrogen bonds involving both backbone and side chains, whereas the marginal stability of the A␤-fibrils is largely due to the formation of weak dispersion interaction between the hydrophobic side chains. The importance of the network of hydrogen bonds is further illustrated by mutational studies, which show that substitution of the Asn and Gln residues to Ala compromises the Sup35 fibril stability. Despite the similarity in the architecture of the amyloid fibrils, the growth mechanism and stability of the fibrils depend dramatically on the sequence.all-atom simulations ͉ amyloid growth dynamics ͉ growth mechanism of fibrils ͉ sequence-dependent addition process ͉ Sup35 and A␤-peptide A number of neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases and transmissible prion disorders are associated with the formation of amyloid protein fibrils with a characteristic ␤-structure. In addition to proteins directly implicated in diseases, others that are unrelated by sequence or structure also form fibrils rich in ␤-sheet structure (1). These observations make it urgent to understand the molecular basis of amyloid fibril formation (1-3). The structures of the amyloid fibrils share a characteristic cross-␤ motif (4-7) with the peptides (or the proteins) forming extended ␤-strands that span the length of the fibril. Depending on the sequence, the strands in a given sheet are arranged in a parallel or antiparallel manner (8, 9) and lie perpendicular to the fibril axis. The near-universal morphology of the fibrils (without consideration of strains) suggests that the global mechanism that drives their formation from monomers may be similar (3). Indeed, several variations of the nucleated polymerization mechanism (NPM) have been used to account for amyloid fibril formation (10-12). According to the NPM, fluctuations (induced by denaturation stress, for example) lead to monomer conformations that can associate with other monomers to form fluid-like oligomers. If the size of the...

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Effect of Dehydration on the Aggregation Kinetics of Two Amyloid Peptides

Cited by 82 publications

References 61 publications

Modular peptides from the thermoplastic squid sucker ring teeth form amyloid-like cross-β supramolecular networks

Modular peptides from the thermoplastic squid sucker ring teeth form amyloid-like cross-β supramolecular networks

Zinc ions promote Alzheimer Aβ aggregation via population shift of polymorphic states

Dynamics of locking of peptides onto growing amyloid fibrils

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