Studies of the aggregation of an amyloidogenic α-synuclein peptide fragment

2005 ◽  
Vol 33 (5) ◽  
pp. 1113-1115 ◽  
Author(s):  
J. Madine ◽  
A.J. Doig ◽  
A. Kitmitto ◽  
D.A. Middleton
Keyword(s):  
Structural Analysis ◽  
Characteristic Feature ◽  
Neurodegenerative Disorders ◽  
Lewy Bodies ◽  
Structural Features ◽  
Full Length ◽  
Peptide Fragment ◽  
Structural Investigations ◽  
Detailed Structural Analysis ◽  
Β Sheet

The deposition of α-syn (α-synuclein) fibrils in Lewy bodies is a characteristic feature of individuals with neurodegenerative disorders. A peptide comprising the central residues 71–82 of α-syn [α-syn(71–82)] is capable of forming β-sheet-rich, amyloid-like fibrils with similar morphologies to fibrils of the full-length protein, providing a useful model of pathogenic α-syn fibrils that is suitable for detailed structural analysis. We have studied the morphology and gross structural features of α-syn(71–82) fibrils formed under different conditions in order to obtain reliable conditions for producing fibrils for further structural investigations. The results indicate that the rate of aggregation and the morphology of the fibrils formed are sensitive to pH and temperature.

scholarly journals Amyloid fibrils prepared using an acetylated and methyl amidated peptide model of the α-Synuclein NAC 71–82 amino acid stretch contain an additional cross-β structure also found in prion proteins

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Thomas Näsström ◽  
Per Ola Andersson ◽  
Christian Lejon ◽  
Björn C. G. Karlsson
Keyword(s):  
Amino Acid ◽  
Protein Misfolding ◽  
Prion Proteins ◽  
Lewy Bodies ◽  
Amyloid Β ◽  
Full Length ◽  
Aggregation Propensity ◽  
Amino Acid Stretch ◽  
Amidated Peptide ◽  
Β Sheet

Abstract The 71–82 fragment of the non-amyloid-β component (NAC) region of the Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) related protein α-Synuclein, has been reported to be important during protein misfolding. Although reports have demonstrated the importance of this fragment for the aggregation properties of the full-length protein, its exact role in pre-fibrillar oligomerisation, fibrillar growth and morphology has not yet been fully elucidated. Here, we provide evidence that fibrils prepared from an acetylated and methyl amidated peptide of the NAC 71–82 amino acid stretch of α-Synuclein are amyloid and contain, in addition to the cross-β structure detected in the full-length protein fibrils, a cross-β structure previously observed in prion proteins. These results shed light on the aggregation propensity of the NAC 71–82 amino acid stretch of the full-length protein but also the roles of the N- and C-terminal domains of α-Synuclein in balancing this aggregation propensity. The results also suggest that early aggregated forms of the capped NAC 71–82 peptide generated structures were stabilised by an anti-parallel and twisted β-sheet motif. Due to its expected toxicity, this β-sheet motif may be a promising molecular target for the development of therapeutic strategies for PD and DLB.

scholarly journals Chemical Modification of Combusted Coal Gangue for U(VI) Adsorption: Towards a Waste Control by Waste Strategy

2021 ◽  
Vol 13 (15) ◽  
pp. 8421
Author(s):  
Yuan Gao ◽  
Jiandong Huang ◽  
Meng Li ◽  
Zhongran Dai ◽  
Rongli Jiang ◽  
...  
Keyword(s):  
Structural Analysis ◽  
High Efficiency ◽  
Low Cost ◽  
Chemical Activation ◽  
Cost Effective ◽  
Coal Gangue ◽  
Order Kinetic ◽  
Practical Applications ◽  
Detailed Structural Analysis ◽  
Alkaline Conditions

Uranium mining waste causes serious radiation-related health and environmental problems. This has encouraged efforts toward U(VI) removal with low cost and high efficiency. Typical uranium adsorbents, such as polymers, geopolymers, zeolites, and MOFs, and their associated high costs limit their practical applications. In this regard, this work found that the natural combusted coal gangue (CCG) could be a potential precursor of cheap sorbents to eliminate U(VI). The removal efficiency was modulated by chemical activation under acid and alkaline conditions, obtaining HCG (CCG activated with HCl) and KCG (CCG activated with KOH), respectively. The detailed structural analysis uncovered that those natural mineral substances, including quartz and kaolinite, were the main components in CCG and HCG. One of the key findings was that kalsilite formed in KCG under a mild synthetic condition can conspicuous enhance the affinity towards U(VI). The best equilibrium adsorption capacity with KCG was observed to be 140 mg/g under pH 6 within 120 min, following a pseudo-second-order kinetic model. To understand the improved adsorption performance, an adsorption mechanism was proposed by evaluating the pH of uranyl solutions, adsorbent dosage, as well as contact time. Combining with the structural analysis, this revealed that the uranyl adsorption process was mainly governed by chemisorption. This study gave rise to a utilization approach for CCG to obtain cost-effective adsorbents and paved a novel way towards eliminating uranium by a waste control by waste strategy.

Structural insights into the repair mechanism of AGT for methyl-induced DNA damage

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Rajendra P. Koirala ◽  
Rudramani Pokhrel ◽  
Prabin Baral ◽  
Purushottam B. Tiwari ◽  
Prem P. Chapagain ◽  
...  
Keyword(s):  
Covalent Bond ◽  
Cancer Therapeutics ◽  
Md Simulations ◽  
Structural Features ◽  
Umbrella Sampling ◽  
Repair Mechanism ◽  
Structural Investigations ◽  
Methylated Dna ◽  
Dna Base ◽  
Dna Alkyltransferase

Abstract Methylation induced DNA base-pairing damage is one of the major causes of cancer. O6-alkylguanine-DNA alkyltransferase (AGT) is considered a demethylation agent of the methylated DNA. Structural investigations with thermodynamic properties of the AGT-DNA complex are still lacking. In this report, we modeled two catalytic states of AGT-DNA interactions and an AGT-DNA covalent complex and explored structural features using molecular dynamics (MD) simulations. We utilized the umbrella sampling method to investigate the changes in the free energy of the interactions in two different AGT-DNA catalytic states, one with methylated GUA in DNA and the other with methylated CYS145 in AGT. These non-covalent complexes represent the pre- and post-repair complexes. Therefore, our study encompasses the process of recognition, complex formation, and separation of the AGT and the damaged (methylated) DNA base. We believe that the use of parameters for the amino acid and nucleotide modifications and for the protein-DNA covalent bond will allow investigations of the DNA repair mechanism as well as the exploration of cancer therapeutics targeting the AGT-DNA complexes at various functional states as well as explorations via stabilization of the complex.

scholarly journals The crystal structure of the first ether solvate of hexaphenyldistannane [(Ph3Sn)2 • 2 THF]

2020 ◽  
Vol 43 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Jonathan O. Bauer
Keyword(s):  
Crystal Structure ◽  
Inclusion Compounds ◽  
Molecular Crystal ◽  
Structural Features ◽  
Structural Investigations ◽  
Crystal Solvates

AbstractStructural investigations of molecular crystal solvates can provide important information for the targeted crystallization of particular inclusion compounds. Here, the crystal structure of the first ether solvate of hexaphenyldistannane [(Ph3Sn)2 • 2 THF] is reported. Structural features in terms of host-guest interactions and in the context of the previously reported polymorphs and solvates of (Ph3Sn)2 are discussed.

Structural analysis of the full-length human LRRK2

Cell ◽  
2021 ◽  
Author(s):  
Alexander Myasnikov ◽  
Hanwen Zhu ◽  
Patricia Hixson ◽  
Boer Xie ◽  
Kaiwen Yu ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Full Length

Peroxisomal multifunctional enzyme type 2 from the fruitfly: dehydrogenase and hydratase act as separate entities, as revealed by structure and kinetics

2011 ◽  
Vol 435 (3) ◽  
pp. 771-781 ◽  
Author(s):  
Tatu J. K. Haataja ◽  
M. Kristian Koski ◽  
J. Kalervo Hiltunen ◽  
Tuomo Glumoff
Keyword(s):  
Crystal Structure ◽  
Saccharomyces Cerevisiae ◽  
Drosophila Melanogaster ◽  
Structural Features ◽  
Full Length ◽  
Multifunctional Enzyme ◽  
Domain Composition ◽  
Substrate Channelling

All of the peroxisomal β-oxidation pathways characterized thus far house at least one MFE (multifunctional enzyme) catalysing two out of four reactions of the spiral. MFE type 2 proteins from various species display great variation in domain composition and predicted substrate preference. The gene CG3415 encodes for Drosophila melanogaster MFE-2 (DmMFE-2), complements the Saccharomyces cerevisiae MFE-2 deletion strain, and the recombinant protein displays both MFE-2 enzymatic activities in vitro. The resolved crystal structure is the first one for a full-length MFE-2 revealing the assembly of domains, and the data can also be transferred to structure–function studies for other MFE-2 proteins. The structure explains the necessity of dimerization. The lack of substrate channelling is proposed based on both the structural features, as well as by the fact that hydration and dehydrogenation activities of MFE-2, if produced as separate enzymes, are equally efficient in catalysis as the full-length MFE-2.

Structural analysis of amyloid ? peptide fragment (25-35) in different microenvironments

Biopolymers ◽  
2004 ◽  
Vol 76 (5) ◽  
pp. 421-434 ◽  
Author(s):  
Ganesh Shanmugam ◽  
Rajadas Jayakumar
Keyword(s):  
Structural Analysis ◽  
Amyloid Peptide ◽  
Peptide Fragment

scholarly journals Detailed Structural Analysis of Lipids Directly on Tissue Specimens Using a MALDI-SpiralTOF-Reflectron TOF Mass Spectrometer

PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e37107 ◽  
Author(s):  
Shuichi Shimma ◽  
Ayumi Kubo ◽  
Takaya Satoh ◽  
Michisato Toyoda
Keyword(s):  
Structural Analysis ◽  
Mass Spectrometer ◽  
Detailed Structural Analysis ◽  
Tissue Specimens

scholarly journals Mutational activation of c-raf-1 and definition of the minimal transforming sequence.

1990 ◽  
Vol 10 (6) ◽  
pp. 2503-2512 ◽  
Author(s):  
G Heidecker ◽  
M Huleihel ◽  
J L Cleveland ◽  
W Kolch ◽  
T W Beck ◽  
...  
Keyword(s):  
Structural Features ◽  
Kinase Domain ◽  
Full Length ◽  
Wild Type ◽  
Amino Terminal ◽  
Raf Kinase ◽  
Rich Domain ◽  
Binding Residue ◽  
Transforming Activity ◽  
Mutational Activation

A series of wild-type and mutant raf genes was transfected into NIH 3T3 cells and analyzed for transforming activity. Full-length wild-type c-raf did not show transforming activity. Two types of mutations resulted in oncogenic activity similar to that of v-raf: truncation of the amino-terminal half of the protein and fusion of the full-length molecule to gag sequences. A lower level of activation was observed for a mutant with a tetrapeptide insertion mapping to conserved region 2 (CR2), a serine- and threonine-rich domain located 100 residues amino-terminal of the kinase domain. To determine essential structural features of the transforming region of raf, we analyzed point and deletion mutants of v-raf. Substitutions of Lys-56 modulated the transforming activity, whereas mutation of Lys-53, a putative ATP binding residue, abolished it. Deletion analysis established that the minimal transforming sequence coincided precisely with CR3, the conserved Raf kinase domain. Thus, oncogenic activation of the Raf kinase can be achieved by removal of CR1 and CR2 or by steric distortion and requires retention of an active kinase domain. These findings are consistent with a protein structure model for the nonstimulated enzyme in which the active site is buried within the protein.

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