scholarly journals A short commentary on indents and edges of β-sheets

2019 ◽  
Author(s):  
Harshavardhan Khare ◽  
Suryanarayanarao Ramakumar
Keyword(s):  
Short Length ◽  
The Other ◽  
Stacking Interactions ◽  
Design Strategies ◽  
Hydrophobic Residues ◽  
Short Commentary ◽  
Β Sheets ◽  
Folded Proteins ◽  
Polypeptide Chains ◽  
Β Sheet

Abstractβ-sheets in proteins are formed by extended polypeptide chains, called β-strands. While there is a general consensus on two types of β-strands, viz. ‘edge strands’ (or ‘edges’) and ‘inner strands’ (or ‘central strands’), the possibility of distinguishing between different regions of inner strands remains less explored. In this paper, we address the portions of inner strands of β-sheets that stick out on either or both sides. We call these portions the ‘indent strands’ or ‘indents’ because they give the typical indented appearance to β-sheets. Similar to the edge strands, the indent strands also have β-bridge partner residues on one side while the other side is still open for backbone hydrogen bonds. Despite this similarity, the indent strands differ from the edge strands in terms of various properties such as β-bulges and amino acid composition due to their localization within β-sheets and therefore within folded proteins to certain extent. The localization of indents and edges within folded proteins seems to govern the strategies deployed to deter unhindered β-sheet propagation through β-strand stacking interactions. Our findings suggest that, edges and indents differ in their strategies to avoid further β-strand stacking. Short length itself is a good strategy to avoid stacking and a majority of indents are two residue or shorter in length. Edge strands on the other hand are overall longer. While long edges are known to use various negative design strategies like β-bulges, prolines, strategically placed charges, inward-pointing charged side chains and loop coverage to avoid further β-strand stacking, long indents seem to favor mechanisms such as enrichment in flexible residues with high solvation potential and depletion in hydrophobic residues in response to their less solvent exposed nature. Such subtle differences between indents and edges could be leveraged for designing novel β-sheet architectures.

scholarly journals Charge guides pathway selection in β-sheet fibrillizing peptide co-assembly

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Dillon T. Seroski ◽  
Xin Dong ◽  
Kong M. Wong ◽  
Renjie Liu ◽  
Qing Shao ◽  
...  
Keyword(s):  
Solid State ◽  
Solid State Nmr ◽  
The Other ◽  
Multicomponent Systems ◽  
Cationic Peptide ◽  
Two Component ◽  
Β Sheets ◽  
Peptide Charge ◽  
Β Sheet

AbstractPeptide co-assembly is attractive for creating biomaterials with new forms and functions. Emergence of these properties depends on the peptide content of the final assembled structure, which is difficult to predict in multicomponent systems. Here using experiments and simulations we show that charge governs content by affecting propensity for self- and co-association in binary CATCH(+/−) peptide systems. Equimolar mixtures of CATCH(2+/2−), CATCH(4+/4−), and CATCH(6+/6−) formed two-component β-sheets. Solid-state NMR suggested the cationic peptide predominated in the final assemblies. The cationic-to-anionic peptide ratio decreased with increasing charge. CATCH(2+) formed β-sheets when alone, whereas the other peptides remained unassembled. Fibrillization rate increased with peptide charge. The zwitterionic CATCH parent peptide, “Q11”, assembled slowly and only at decreased simulation temperature. These results demonstrate that increasing charge draws complementary peptides together faster, favoring co-assembly, while like-charged molecules repel. We foresee these insights enabling development of co-assembled peptide biomaterials with defined content and predictable properties.

scholarly journals Compositional Determinants of Prion Formation in Yeast

2009 ◽  
Vol 30 (1) ◽  
pp. 319-332 ◽  
Author(s):  
James A. Toombs ◽  
Blake R. McCarty ◽  
Eric D. Ross
Keyword(s):  
Amino Acid ◽  
Amino Acid Composition ◽  
Amyloid Formation ◽  
Yeast Prion ◽  
Hydrophobic Residues ◽  
Predictive Methods ◽  
Infectious Proteins ◽  
Β Sheet ◽  
Eukaryotic Genomes

ABSTRACT Numerous prions (infectious proteins) have been identified in yeast that result from the conversion of soluble proteins into β-sheet-rich amyloid-like protein aggregates. Yeast prion formation is driven primarily by amino acid composition. However, yeast prion domains are generally lacking in the bulky hydrophobic residues most strongly associated with amyloid formation and are instead enriched in glutamines and asparagines. Glutamine/asparagine-rich domains are thought to be involved in both disease-related and beneficial amyloid formation. These domains are overrepresented in eukaryotic genomes, but predictive methods have not yet been developed to efficiently distinguish between prion and nonprion glutamine/asparagine-rich domains. We have developed a novel in vivo assay to quantitatively assess how composition affects prion formation. Using our results, we have defined the compositional features that promote prion formation, allowing us to accurately distinguish between glutamine/asparagine-rich domains that can form prion-like aggregates and those that cannot. Additionally, our results explain why traditional amyloid prediction algorithms fail to accurately predict amyloid formation by the glutamine/asparagine-rich yeast prion domains.

scholarly journals Factors involved in the stability of isolated β-sheets: Turn sequence, β-sheet twisting, and hydrophobic surface burial

2004 ◽  
Vol 13 (4) ◽  
pp. 1134-1147 ◽  
Author(s):  
Clara M. Santiveri ◽  
Jorge Santoro ◽  
Manuel Rico ◽  
M. Angeles Jiménez
Keyword(s):  
Hydrophobic Surface ◽  
Β Sheets ◽  
The Stability ◽  
Β Sheet

scholarly journals Crystal structure of 4-({5-[(E)-(3,5-difluorophenyl)diazenyl]-2-hydroxybenzylidene}amino)-2,2,6,6-tetramethylpiperidin-1-oxyl

2015 ◽  
Vol 71 (7) ◽  
pp. 864-866
Author(s):  
Ramazan Tatsız ◽  
Veli T. Kasumov ◽  
Tuncay Tunc ◽  
Tuncer Hökelek
Keyword(s):  
Dihedral Angle ◽  
Three Dimensional ◽  
Chair Conformation ◽  
The Other ◽  
Supramolecular Network ◽  
Stacking Interactions ◽  
Asymmetric Unit ◽  
Compound C ◽  
Benzene Rings ◽  
Independent Molecules

The asymmetric unit of the title compound, C22H25F2N4O2, contains two crystallographically independent molecules. In one molecule, the two benzene rings are oriented at a dihedral angle of 1.93 (10)° and in the other molecule the corresponding dihedral angle is 7.19 (9)°. The piperidine rings in the two molecules adopt a similar distorted chair conformation, and both have pseudo-mirror planes passing through the N—O bonds. An intramolecular O—H...N hydrogen bond between the hydroxy group and the imine N atom is observed in both molecules. In the crystal, weak C—H...O and C—H...F hydrogen bonds, enclosingR22(6) ring motifs, and weak π–π stacking interactions link the molecules into a three-dimensional supramolecular network, with centroid-to-centroid distances between the nearly parallel phenyl and benzene rings of adjacent molecules of 3.975 (2) and 3.782 (2) Å.

scholarly journals Differential functions of FANCI and FANCD2 ubiquitination stabilize ID2 complex on DNA

2020 ◽  
Author(s):  
Martin L. Rennie ◽  
Kimon Lemonidis ◽  
Connor Arkinson ◽  
Viduth K. Chaugule ◽  
Mairi Clarke ◽  
...  
Keyword(s):  
Fanconi Anemia ◽  
Large Scale ◽  
The Other ◽  
Molecular Function ◽  
Post Translational Modifications ◽  
Hydrophobic Residues ◽  
Interstrand Crosslinks ◽  
Double Stranded Dna ◽  
Dna Interstrand Crosslinks ◽  
Lysine Residues

AbstractThe Fanconi Anemia (FA) pathway is a dedicated pathway for the repair of DNA interstrand crosslinks, and which is additionally activated in response to other forms of replication stress. A key step in the activation of the FA pathway is the monoubiquitination of each of the two subunits (FANCI and FANCD2) of the ID2 complex on specific lysine residues. However, the molecular function of these modifications has been unknown for nearly two decades. Here we find that ubiquitination of FANCD2 acts to increase ID2’s affinity for double stranded DNA via promoting/stabilizing a large-scale conformational change in the complex, resulting in a secondary “Arm” ID2 interphase encircling DNA. Ubiquitination of FANCI, on the other hand, largely protects the ubiquitin on FANCD2 from USP1/UAF deubiquitination, with key hydrophobic residues of FANCI’s ubiquitin being important for this protection. In effect, both of these post-translational modifications function to stabilise a conformation in which the ID2 complex encircles DNA.

NMR structure of bucandin, a neurotoxin from the venom of the Malayan krait (Bungarus candidus)

2001 ◽  
Vol 360 (3) ◽  
pp. 539-548 ◽  
Author(s):  
Allan M. TORRES ◽  
R. Manjunatha KINI ◽  
Nirthanan SELVANAYAGAM ◽  
Philip W. KUCHEL
Keyword(s):  
Solution Structure ◽  
Pharmacological Action ◽  
Nmr Structure ◽  
Side Chains ◽  
X Ray ◽  
Nmr Study ◽  
C Terminus ◽  
Mean Structure ◽  
Β Sheets ◽  
Β Sheet

A high-resolution solution structure of bucandin, a neurotoxin from Malayan krait (Bungarus candidus), was determined by 1H-NMR spectroscopy and molecular dynamics. The average backbone root-mean-square deviation for the 20 calculated structures and the mean structure is 0.47 Å (1 Å = 0.1nm) for all residues and 0.24 Å for the well-defined region that spans residues 23–58. Secondary-structural elements include two antiparallel β-sheets characterized by two and four strands. According to recent X-ray analysis, bucandin adopts a typical three-finger loop motif and yet it has some peculiar characteristics that set it apart from other common α-neurotoxins. The presence of a fourth strand in the second antiparallel β-sheet had not been observed before in three-finger toxins, and this feature was well represented in the NMR structure. Although the overall fold of the NMR structure is similar to that of the X-ray crystal structure, there are significant differences between the two structures that have implications for the pharmacological action of the toxin. These include the extent of the β-sheets, the conformation of the region spanning residues 42–49 and the orientation of some side chains. In comparison with the X-ray structure, the NMR structure shows that the hydrophobic side chains of Trp27 and Trp36 are stacked together and are orientated towards the tip of the middle loop. The NMR study also showed that the two-stranded β-sheet incorporated in the first loop, as defined by residues 1–22, and the C-terminus from Asn59, is probably flexible relative to the rest of the molecule. On the basis of the dispositions of the hydrophobic and hydrophilic side chains, the structure of bucandin is clearly different from those of cytotoxins.

Influence of Strand Number on Antiparallel β-Sheet Stability in Designed Three- and Four-stranded β-Sheets

2003 ◽  
Vol 326 (2) ◽  
pp. 553-568 ◽  
Author(s):  
Faisal A. Syud ◽  
Heather E. Stanger ◽  
Heather Schenck Mortell ◽  
Juan F. Espinosa ◽  
John D. Fisk ◽  
...  
Keyword(s):  
Β Sheets ◽  
Β Sheet

The Bβ-sheet in the PAI-1 Molecule Plays an Important Role for Its Stability

2000 ◽  
Vol 83 (06) ◽  
pp. 896-901 ◽  
Author(s):  
Guang-Chao Sui ◽  
Björn Wiman
Keyword(s):  
Amino Acids ◽  
Half Life ◽  
Ph Dependence ◽  
The Other ◽  
Wild Type ◽  
E Coli ◽  
Reactive Center ◽  
The Stability ◽  
Β Sheet ◽  
Pai 1

SummaryWe have investigated the B β-sheet in PAI-1 regarding its role for the stability of the molecule. The residues from His219 to Tyr241 (except for Gly230 and Pro240), covering the s2B and s3B strands, and in addition His185 and His190 were substituted by amino acids with opposite properties. The 23 generated single-site changed mutants and also wild type PAI-1 (wtPAI-1) were expressed in E. coli. Subsequently they were purified by heparin-Sepharose and anhydrotrypsin agarose affinity chromatographies. The stability of the purified PAI-1 variants was analyzed at 37° C and at different pHs (5.5, 6.5 or 7.5). At pH 7.5 and 37° C, single substitutions of the residues in the central portions of both strands 2 and 3 in the B β-sheet (Ile223 to Leu226 on s2B and Met235 to Ile237 on s3B), caused a significant decrease in stability, yielding half-lives of about 10–25% as compared to wtPAI-1. On the other hand, mutations at both sides of the central portion of the B β-sheet (Tyr221, Asp222, Tyr228 and Thr232) frequently resulted in an increased PAI-1 stability (up to 7-fold). While wtPAI-1 exhibited prolonged half-lives at pH 6.5 and 5.5, the PAI-1 variant Y228S was more stable at neutral pH (half-life of 9.6 h at pH 7.5) as compared to its half-life at pH 5.5 (1.1 h). One of the 4 modified histidine residues (His229) resulted in a variant with a clearly affected stability as a function of pH, suggesting that it may, at least in part, be of importance for the pH dependence of the PAI-1 stability. Thus, our data demonstrate that the B β-sheet is of great importance for the stability of the molecule. Modifications in this part causes decreased or increased stability in a certain pattern, suggesting effects on the insertion rate of the reactive center loop into the A β-sheet of the molecule.

Religion and Constitutional Practices in Asia: Five ‘Cs’ for Reflection

2018 ◽  
Vol 13 (2) ◽  
pp. 219-225
Author(s):  
Arif A JAMAL
Keyword(s):  
Case Studies ◽  
Comparative Law ◽  
The Other ◽  
Special Issue ◽  
Other Hand ◽  
Short Commentary ◽  
Five Cs ◽  
The One ◽  
The Individual

AbstractIn considering the articles in this Special Issue, I am struck by the importance of a set of factors that, in my view, both run through the articles like a leitmotif, as well as shape the major ‘take away’ lesson(s) from the articles. In this short commentary, I elaborate on these factors and the lesson(s) to take from them through five ‘Cs’: context; complexity; contestation; the framework of constitutions; and the role of comparative law. The first three ‘Cs’ are lessons from the case studies of the articles themselves, while the second two ‘Cs’ are offered as lessons to help take the dialogue forward. Fundamentally, these five ‘Cs’ highlight the importance of the articles in this Special Issue and the conference from which they emerged on the one hand, while on the other hand, also making us aware of what are the limits of what we should conclude from the individual articles. In other words, taken together, the five ‘Cs’ are, one might say, lessons about lessons.

scholarly journals Rippled β-Sheet Formation by an Amyloid-β Fragment Indicates Expanded Scope of Sequence Space for Enantiomeric β-Sheet Peptide Coassembly

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1983 ◽  
Author(s):  
Jennifer M. Urban ◽  
Janson Ho ◽  
Gavin Piester ◽  
Riqiang Fu ◽  
Bradley L. Nilsson
Keyword(s):  
Sequence Space ◽  
Self Assembly ◽  
Solid State Nmr ◽  
Amyloid Β ◽  
Amino Acid Residues ◽  
Hydrophobic Amino Acid ◽  
Amphipathic Peptide ◽  
Sequence Patterns ◽  
Β Sheets ◽  
Β Sheet

In 1953, Pauling and Corey predicted that enantiomeric β-sheet peptides would coassemble into so-called “rippled” β-sheets, in which the β-sheets would consist of alternating l- and d-peptides. To date, this phenomenon has been investigated primarily with amphipathic peptide sequences composed of alternating hydrophilic and hydrophobic amino acid residues. Here, we show that enantiomers of a fragment of the amyloid-β (Aβ) peptide that does not follow this sequence pattern, amyloid-β (16–22), readily coassembles into rippled β-sheets. Equimolar mixtures of enantiomeric amyloid-β (16–22) peptides assemble into supramolecular structures that exhibit distinct morphologies from those observed by self-assembly of the single enantiomer pleated β-sheet fibrils. Formation of rippled β-sheets composed of alternating l- and d-amyloid-β (16–22) is confirmed by isotope-edited infrared spectroscopy and solid-state NMR spectroscopy. Sedimentation analysis reveals that rippled β-sheet formation by l- and d-amyloid-β (16–22) is energetically favorable relative to self-assembly into corresponding pleated β-sheets. This work illustrates that coassembly of enantiomeric β-sheet peptides into rippled β-sheets is not limited to peptides with alternating hydrophobic/hydrophilic sequence patterns, but that a broader range of sequence space is available for the design and preparation of rippled β-sheet materials.

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