scholarly journals Exceptional aggregation propensity of amino acids in polyglutamine amino-acid-homopolymer

2020 ◽  
Author(s):  
Rahul Mishra ◽  
Ashwani K. Thakur
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Van Der Waals ◽  
Physicochemical Characteristic ◽  
Aggregation Behavior ◽  
Human Proteome ◽  
Van Der Waals Volume ◽  
Aggregation Propensity ◽  
Starting Point ◽  
Β Sheet

AbstractSimilar aggregation and β-sheet propensity of amino acids in globular proteins and amyloids, suggests comparable principles of their formation. Here we show that during the process of aggregation into amyloid-like fibers, these rules are not the same in an amino-acid-homopolymer (AAHP) polyglutamine (PolyGln). An aggregation kinetic analysis on nine-point mutants of a forty-six long PolyGln peptide was carried in physiological conditions. At the dynamic equilibrium state of aggregation, critical-concentration derived free-energy differences, signifying aggregation propensity of incorporated amino acids were obtained. None of the obtained propensities correlated with existing conventional aggregation and β-sheet propensities of the amino acids in proteins and amyloids. Further, the differential aggregation behavior of all the peptides only correlated with van der Waals volume of the incorporated amino acid and not with any other physicochemical characteristic of amino acids. The new rules obtained from PolyGln AAHP provide an opportunity to explore physiological relevance of a mutation within AAHP in human proteome. Additionally, this study opens up new avenues for protein model design exploring folding and aggregation behavior of other amino-acid-homopolymer (AAHP) existing in the human proteome.SignificanceMutational analysis within PolyGln sequences adds to the knowledge of unique aggregation propensities of amino acids within PolyGln AAHP. This study highlights the importance of van der Waals volume in dictating stability-instability of an aggregation fold and in turn aggregation kinetics and thermodynamic stability of aggregates. The analysis signifies the role of Gln-Gln interlocking system within PolyGln folding motif and extent of disruption caused by van der Waals volume of an amino acid. The results can be taken as a starting point to evaluate the possible impact of amino acid insertions in PolyGln stretches of other proteins. It also opens opportunities to study the structural and functional relationship of other AAHPS for their unique folding and aggregation behavior. Learning outcome can be utilized as a bottom–up approach to design amyloid biomaterial with different strengths for biomedical applications.

scholarly journals Structural and Physical Properties of a Necrosis-Inducing Toxin from Pyrenophora tritici-repentis

1997 ◽  
Vol 87 (2) ◽  
pp. 154-160 ◽  
Author(s):  
Hui-Fen Zhang ◽  
Leonard J. Francl ◽  
James G. Jordahl ◽  
Steven W. Meinhardt
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Structure Prediction ◽  
Secondary Structure Prediction ◽  
Cd Spectroscopy ◽  
Tan Spot ◽  
Pyrenophora Tritici Repentis ◽  
Membrane Adhesion ◽  
Α Helix ◽  
Β Sheet

Cultivar-specific toxic metabolites of Pyrenophora tritici-repentis are involved in the appearance of necrotic and chlorotic foliar lesions characteristic of tan spot. A P. tritici-repentis necrosis-inducing toxin, Ptr necrosis toxin, was purified from isolate 86-124, sequenced by gas-phase amino acid microsequencing, and characterized by circular dichroism (CD) spectroscopy and isoelectric focusing. The purified protein had a similar amino acid composition and molecular weight as previously reported. Analysis of the CD spectrum from 178 to 250 nm indicated a protein consisting of 13% α-helix, 36% antiparallel β-sheet, 25% turns, and 25% other structures. The Ptr necrosis toxin from isolate 86-124 has an isoelectric point near pH 10. Using overlapping proteolytic fragments obtained from the toxin, a sequence of 101 continuous amino acids was obtained, but the amino terminus was blocked and 9 to 16 amino acids could not be sequenced. Secondary structure prediction based on the amino acid sequence indicated a β-sheet protein with little α-helix, which is in agreement with the structure determined by CD spectroscopy. Sequence analysis indicated the presence of a possible membrane adhesion site and several possible phosphorylation sites that may be involved in phytotoxicity.

scholarly journals Calculation and Analysis of Fractal Descriptors for Protein Amino Acids in Various Conformational States

2018 ◽  
Vol 1 (3) ◽  
pp. e00070
Author(s):  
V.Yu. Grigorev ◽  
L.D. Grigoreva
Keyword(s):  
Amino Acids ◽  
Conformational Transition ◽  
Van Der Waals ◽  
Conformational State ◽  
Conformational States ◽  
Protein Amino Acids ◽  
Α Helix ◽  
Β Sheet ◽  
Fractal Descriptor

A series of 20 proteinogenic amino acids was studied. Four types of fractal descriptors for 2 conformational states are calculated: α-helix and 1-strand β-sheet. Based on the analysis of the results obtained, it is established that when the conformational state of the amino acids (α-helix→β-sheet) changes, significant changes in the fractal descriptor Dtot, in the calculation of which all the atoms of the molecule are used, are not observed. However, the more specific descriptors Dval, Dvdw and Dunb, which reflect the aggregate of valence-coupled, van der Waals contact and unbound atoms, respectively, are more sensitive to the conformational transition. The increase Dval, Dvdw and the decrease Dunb values were established for a series of 7 amino acids.

Effect of Pulsed Electric Field on Microstructure of Some Amino Acid Group of Soy Protein Isolates

2014 ◽  
Vol 10 (1) ◽  
pp. 113-120 ◽  
Author(s):  
Yan-Yan Liu ◽  
Ying Zhang ◽  
Xin-An Zeng ◽  
H. El-Mashad ◽  
Zhong-Li Pan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Electric Field ◽  
Disulfide Bond ◽  
Soy Protein ◽  
Pulsed Electric Field ◽  
Protein Isolates ◽  
Pulse Intensity ◽  
Soy Protein Isolates ◽  
Β Sheet

Abstract The effect of a pulsed electric field (PEF) on the microstructure of some amino acids was studied. Raman spectrum was used to determine the effect of PEF on tyrosine, tryptophan, proline residues, histidine, arginine, aliphatic amino acid, disulfide bond, and polypeptide backbone in soy protein isolates (SPI). Results suggested that increasing the intensity of PEF gradually to 50 kV cm−1 led to a reduction in gauche C–S conformation of CCSSCC dihedral angles. The increase of the PEF intensity caused an increase in the gauche–gauche–gauche conformation of the disulfide bond accompanying a decrease in α-helix and β-sheet and an increase in antiparallel β-sheet and disorder structure. A critical pulse intensity of 30 kV cm−1 was observed for unfolding and reassembling of SPI, which was verified in our previous study (Liu et al., Eur Food Res Technol 233:841–50). When the pulse intensity gradually increased to around 30 kV cm−1, the exposure of tyrosine and tryptophan, the vibration of CH2 wagging in proline and CH2 in the midazole ring of histidine, the vibration of C—H bending and C—N stretching inside a charged arginine, and asymmetric H—C—H bending deformation vibration in CH2 and CH3 groups in aromatic and aliphatic amino acids gradually increased, suggesting an unfolding of protein molecules. When the pulse intensity continually increased from 30 to 50 kV cm−1, the microstructure of all above amino acids decreased due to the reassembly of unfolding proteins.

scholarly journals Effect of L- to D-Amino Acid Substitution on Stability and Activity of Antitumor Peptide RDP215 against Human Melanoma and Glioblastoma

2021 ◽  
Vol 22 (16) ◽  
pp. 8469
Author(s):  
Theresa Maxian ◽  
Lisa Gerlitz ◽  
Sabrina Riedl ◽  
Beate Rinner ◽  
Dagmar Zweytick
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Cationic Peptides ◽  
Model Studies ◽  
Amino Acid Variant ◽  
Sds Page ◽  
Membrane Effects ◽  
2D And 3D ◽  
Β Sheet

The study investigates the antitumor effect of two cationic peptides, R-DIM-P-LF11-215 (RDP215) and the D-amino acid variant 9D-R-DIM-P-LF11-215 (9D-RDP215), targeting the negatively charged lipid phosphatidylserine (PS) exposed by cancer cells, such as of melanoma and glioblastoma. Model studies mimicking cancer and non-cancer membranes revealed the specificity for the cancer-mimic PS by both peptides with a slightly stronger impact by the D-peptide. Accordingly, membrane effects studied by DSC, leakage and quenching experiments were solely induced by the peptides when the cancer mimic PS was present. Circular dichroism revealed a sole increase in β-sheet conformation in the presence of the cancer mimic for both peptides; only 9D-RDP215 showed increased structure already in the buffer. Ex vitro stability studies by SDS-PAGE as well as in vitro with melanoma A375 revealed a stabilizing effect of D-amino acids in the presence of serum, which was also confirmed in 2D and 3D in vitro experiments on glioblastoma LN-229. 9D-RDP215 was additionally able to pass a BBB model, whereupon it induced significant levels of cell death in LN-229 spheroids. Summarized, the study encourages the introduction of D-amino acids in the design of antitumor peptides for the improvement of their stable antitumor activity.

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 Hybrid approach to analysis of β-sheet structures based on signal processing and statistical consideration

2010 ◽  
Vol 467 (2128) ◽  
pp. 1052-1072
Author(s):  
V. Vojisavljevic ◽  
E. Pirogova ◽  
D. M. Davidovic ◽  
I. Cosic
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Protein Design ◽  
Hybrid Approach ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Spectra Analysis ◽  
Sheet Structure ◽  
The Relationship ◽  
Β Sheet

A number of biotechnology applications are based on protein design. For this design, the relationship between a protein’s primary structure and its conformation is of vital importance. A β-sheet is a common feature of a protein’s two-dimensional structure; therefore, elucidating the principles governing β-sheet structure and its stability is critical for understanding the protein-folding process. In the three-dimensional representation of protein molecules, C α carbon coordinates (carbon atom immediately adjacent to the carboxylate group) have often been employed instead of the complete set of coordinates for the corresponding residues. Using the C α carbon coordinates, we showed that particular amino acids are not randomly distributed within a β-sheet structure. On the basis of a new statistical approach for the analysis of a spatial distribution of amino acids in a protein, presented by their physico-chemical parameters, the electron–ion interaction potential (EIIP) and hydrophobicity, are described here. The relationship between amino acid positions inside the β-sheet and the EIIP and hydrophobicity parameters was established. The correlation between amino acid propensities related to the β-sheet was examined using multiple cross-spectra analysis. We also applied the continuous wavelet transform for the analysis of selected β-sheet structures using the EIIP and hydrophobicity parameters. The findings provide new insight into conformational propensities of amino acids for the adaption of β-sheet structures.

scholarly journals A Capped Peptide of the Aggregation Prone NAC 71–82 Amino Acid Stretch of α-Synuclein Folds into Soluble β-Sheet Oligomers at Low and Elevated Peptide Concentrations

2020 ◽  
Vol 21 (5) ◽  
pp. 1629 ◽  
Author(s):  
Thomas Näsström ◽  
Jörgen Ådén ◽  
Fumina Shibata ◽  
Per Ola Andersson ◽  
Björn C.G. Karlsson
Keyword(s):  
Amino Acid ◽  
Prion Proteins ◽  
Lewy Bodies ◽  
Amyloid Β ◽  
Aggregation Kinetics ◽  
Lewy Neurites ◽  
Aggregation Propensity ◽  
Amino Acid Stretch ◽  
Dynamics Simulations ◽  
Β Sheet

Although Lewy bodies and Lewy neurites are hallmarks of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), misfolded α-synuclein oligomers are nowadays believed to be key for the development of these diseases. Attempts to target soluble misfolded species of the full-length protein have been limited so far, probably due to the fast aggregation kinetics and burial of aggregation prone segments in final cross-β-sheet fibrils. A previous characterisation study of fibrils prepared from a capped peptide of the non-amyloid β-component (NAC) 71–82 amino acid stretch of α-synuclein demonstrated an increased aggregation propensity resulting in a cross-β-structure that is also found in prion proteins. From this, it was suggested that capped NAC 71–82 peptide oligomers would provide interesting motifs with a capacity to regulate disease development. Here, we demonstrated, from a series of circular dichroism spectroscopic measurements and molecular dynamics simulations, the molecular-environment-sensitive behaviour of the capped NAC 71–82 peptide in a solution phase and the formation of β-sheet oligomeric structures in the supernatant of a fibrillisation mixture. These results highlighted the use of the capped NAC 71–82 peptide as a motif in the preparation of oligomeric β-sheet structures that potentially could be used in therapeutic strategies in the fight against progressive neurodegenerative disorders, such as PD and DLB.

scholarly journals Amino Acid Content in Onions as Potential Fingerprints of Geographical Origin: The Case of Rossa da Inverno sel. Rojo Duro

2018 ◽  
Author(s):  
Federica Ianni ◽  
Antonella Lisanti ◽  
Maura Marinozzi ◽  
Emidio Camaioni ◽  
Lucia Pucciarini ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Geographical Origin ◽  
Amino Acid Content ◽  
Amino Acid Profile ◽  
Amino Acid Mixture ◽  
Hplc Method ◽  
Acid Mixture ◽  
Umbria Region ◽  
Starting Point

In the frame of a broader project, we were interested at comparing the amino acid profile in a specific variety of onion, Rossa da inverno sel. Rojo Duro, produced in two different Italian sites: Cannara (Umbria region) and Imola (Emilia Romagna region). In both places, onions were cultivated and harvested in the same way, and irrigated by water sprinkler method. A further group of Cannara onions, growth by microirrigation, was also evaluated. After the extraction of free amino acid mixture from onion samples, an ion-pairing RP-HPLC method allowed the separation and the evaporative light scattering detection of almost all underivatized proteinogenic amino acids. However, only the peaks corresponding to Leu, Phe, Trp, were present in all the investigated samples and unaffected from matrix interfering peaks. The application of the beeswarm/box plots with the ANOVA/TukeyHSD statistical approach revealed a content of Leu and Phe markedly influenced by the geographical origin of the onions, while not by the irrigation procedure. The developed HPLC method was validated in terms of specificity, linearity, LOD and LOQ, accuracy and precision, before the quantitative assay of Leu, Phe and Trp in the onion samples. Although further studies are necessary, these preliminary findings can represent a good starting point for considering the quantity of specific amino acids in the Rossa da inverno sel. Rojo Duro variety as a fingerprint of its geographical origin. In principle, the developed approach might be applied to other onion varieties, thus contributing to their characterization and traceability, also contributing to limit commercial frauds.

scholarly journals Self and Nonself Short Constituent Sequences of Amino Acids in the SARS-CoV-2 Proteome for Vaccine Development

COVID ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 555-574
Author(s):  
Joji M. Otaki ◽  
Wataru Nakasone ◽  
Morikazu Nakamura
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Human Proteome ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Amino Acid Residues

Current SARS-CoV-2 vaccines take advantage of the viral spike protein required for infection in humans. Considering that spike proteins may contain both “self” and “nonself” sequences (sequences that exist in the human proteome and those that do not, respectively), nonself sequences are likely to be better candidate epitopes than self sequences for vaccines to efficiently eliminate pathogenic proteins and to reduce the potential long-term risks of autoimmune diseases. This viewpoint is likely important when one considers that various autoantibodies are produced in COVID-19 patients. Here, we comprehensively identified self and nonself short constituent sequences (SCSs) of 5 amino acid residues in the proteome of SARS-CoV-2. Self and nonself SCSs comprised 91.2% and 8.8% of the SARS-CoV-2 proteome, respectively. We identified potentially important nonself SCS clusters in the receptor-binding domain of the spike protein that overlap with previously identified epitopes of neutralizing antibodies. These nonself SCS clusters may serve as functional epitopes for effective, safe, and long-term vaccines against SARS-CoV-2 infection. Additionally, analyses of self/nonself status changes in mutants revealed that the SARS-CoV-2 proteome may be evolving to mimic the human proteome. Further SCS-based proteome analyses may provide useful information to predict epidemiological dynamics of the current COVID-19 pandemic.

Dietary intake of tryptophan tied emotion-related impulsivity in humans

2019 ◽  
pp. 1-8 ◽  
Author(s):  
Florian Javelle ◽  
Descartes Li ◽  
Philipp Zimmer ◽  
Sheri L. Johnson
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Food Intake ◽  
Essential Amino Acid ◽  
Food Habits ◽  
Psychological Disorder ◽  
Serotonin Synthesis ◽  
Amino Acid Tryptophan ◽  
Pass Through ◽  
Three Factor

Abstract. Emotion-related impulsivity, defined as the tendency to say or do things that one later regret during periods of heightened emotion, has been tied to a broad range of psychopathologies. Previous work has suggested that emotion-related impulsivity is tied to an impaired function of the serotonergic system. Central serotonin synthesis relies on the intake of the essential amino acid, tryptophan and its ability to pass through the blood brain barrier. Objective: The aim of this study was to determine the association between emotion-related impulsivity and tryptophan intake. Methods: Undergraduate participants (N = 25, 16 women, 9 men) completed a self-rated measure of impulsivity (Three Factor Impulsivity Index, TFI) and daily logs of their food intake and exercise. These data were coded using the software NutriNote to evaluate intakes of tryptophan, large neutral amino acids, vitamins B6/B12, and exercise. Results: Correlational analyses indicated that higher tryptophan intake was associated with significantly lower scores on two out of three subscales of the TFI, Pervasive Influence of Feelings scores r =  –.502, p < . 010, and (lack-of) Follow-Through scores, r =  –.407, p < . 050. Conclusion: Findings provide further evidence that emotion-related impulsivity is correlated to serotonergic indices, even when considering only food habits. It also suggests the need for more research on whether tryptophan supplements might be beneficial for impulsive persons suffering from a psychological disorder.

Sign in / Sign up

Export Citation Format

Share Document