From the Evolution of Protein Sequences Able to Resist Self-Assembly to the Prediction of Aggregation Propensity

2017 ◽  
pp. 1-47 ◽  
Author(s):  
F. Bemporad ◽  
M. Ramazzotti
Keyword(s):  
Self Assembly ◽  
Protein Sequences ◽  
Aggregation Propensity

scholarly journals A3D 2.0 update for the prediction and optimization of protein solubility

2021 ◽  
Author(s):  
Jordi Pujols ◽  
Valentín Iglesias ◽  
Jaime Santos ◽  
Aleksander Kuriata ◽  
Sebastian Kmiecik ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Protein Solubility ◽  
Protein Sequences ◽  
Cost Effective ◽  
Computational Pipeline ◽  
Protein Surfaces ◽  
Computational Approaches ◽  
Aggregation Propensity ◽  
Restful Service ◽  
Protein Redesign

AbstractProtein aggregation propensity is a property imprinted in protein sequences and structures, being associated with the onset of human diseases and limiting the implementation of protein-based biotherapies. Computational approaches stand as cost-effective alternatives for reducing protein aggregation and increasing protein solubility. AGGRESCAN 3D (A3D) is a structure-based predictor of aggregation that takes into account the conformational context of a protein, aiming to identify aggregation-prone regions exposed in protein surfaces. Here we inspect the updated 2.0 version of the algorithm, which extends the application of A3D to previously inaccessible proteins and incorporates new modules to assist protein redesign. Among these features, the new server includes stability calculations and the possibility to optimize protein solubility using an experimentally validated computational pipeline. Finally, we employ defined examples to navigate the A3D RESTful service, a routine to handle extensive protein collections. Altogether, this work is conceived to train and assist A3D non-experts in the study of aggregation-prone regions and protein solubility redesign.

scholarly journals Capturing Aβ42 aggregation in the cell

2019 ◽  
Vol 294 (5) ◽  
pp. 1488-1489 ◽  
Author(s):  
Francesco Bemporad ◽  
Cristina Cecchi ◽  
Fabrizio Chiti
Keyword(s):  
Self Assembly ◽  
Imaging Techniques ◽  
Living Cells ◽  
Protein Processing ◽  
The Arctic ◽  
Amyloid Protein ◽  
Aggregation Propensity ◽  
Protein Deposition ◽  
Aβ Aggregation ◽  
First Time

Novel imaging techniques with ever-increasing resolution are invaluable tools for the study of protein deposition, as they allow the self-assembly of proteins to be directly investigated in living cells. For the first time, the acceleration in Aβ42 aggregation induced by the Arctic mutation was monitored in cells, revealing a number of distinct morphologies that form sequentially. This approach will help discriminate the impacts of mutations on amyloid protein processing, Aβ aggregation propensity, and other mechanistic outcomes.

scholarly journals Introduction of a Lysine Residue Promotes Aggregation of Temporin L in Lipopolysaccharides and Augmentation of Its Antiendotoxin Property

2013 ◽  
Vol 57 (6) ◽  
pp. 2457-2466 ◽  
Author(s):  
Saurabh Srivastava ◽  
Jimut Kanti Ghosh
Keyword(s):  
Antimicrobial Peptide ◽  
Self Assembly ◽  
Biological Properties ◽  
Lysine Residue ◽  
Aqueous Environment ◽  
Oligomeric State ◽  
Aggregation Propensity ◽  
Hydrophobic Nature

ABSTRACTTemporin L (TempL) is a 13-residue frog antimicrobial peptide that shows moderate bactericidal activity and antiendotoxin properties in macrophages. We envisioned that, due to its very hydrophobic nature, the peptide might fail to show its desired biological properties. It was predicted by employing the available algorithms that the replacement of a glutamine by lysine at position 3 could appreciably reduce its aggregation propensity in an aqueous environment. In order to investigate the structural, functional, and biological consequences of replacement of glutamine by lysine at its third position, TempL and the corresponding analog, Q3K-TempL, was synthesized and characterized. Introduction of the lysine residue significantly promoted the self-assembly and oligomeric state of TempL in lipopolysaccharide (LPS). Q3K-TempL exhibited augmented binding to LPS and also dissociated LPS aggregates with greater efficacy than TempL. Further, Q3K-TempL inhibited the LPS-induced proinflammatory cytokines in rat primary macrophagesin vitroandin vivoin BALB/c mice with greater efficacy than TempL. The results showed that a simple amino acid substitution in a short hydrophobic antimicrobial peptide, TempL, enhanced its antiendotoxin properties and illustrate a plausible correlation between its aggregation properties in LPS and LPS detoxification activity.

scholarly journals The hunt for ancient prions: Archaeal prion-like domains form amyloids and substitute for yeast prion domains

2020 ◽  
Author(s):  
Tomasz Zajkowski ◽  
Michael D. Lee ◽  
Shamba S. Mondal ◽  
Amanda Carbajal ◽  
Robert Dec ◽  
...  
Keyword(s):  
Self Assembly ◽  
Information Transfer ◽  
Amyloid Fibrils ◽  
Common Ancestor ◽  
Protein Sequences ◽  
Yeast Prion ◽  
Last Universal Common Ancestor ◽  
Universal Common Ancestor ◽  
Domains Of Life

AbstractPrions are proteins capable of acquiring an alternate conformation that can then induce additional copies to adopt this same alternate conformation. Although initially discovered in relation to mammalian disease, subsequent studies have revealed the presence of prions in Bacteria and Viruses, suggesting an ancient evolutionary origin. Here we explore whether prions exist in Archaea - the last domain of life left unexplored with regard to prions. After searching for potential prion-forming protein sequences computationally, we tested candidates in vitro and in organisms from the two other domains of life: Escherichia coli and Saccharomyces cerevisiae. Out of the 16 candidate prion-forming domains tested, 8 bound to amyloid-specific dye, and six acted as protein-based elements of information transfer, driving non-Mendelian patterns of inheritance. We additionally identified short peptides from archaeal prion candidates that can form amyloid fibrils independently. Candidates that tested positively in our assays had significantly higher tyrosine and phenylalanine content than candidates that tested negatively, suggesting that the presence of these amino acids may help distinguish functional prion domains from nonfunctional ones. Our data establish the presence of amyloid-forming prion-like domains in Archaea. Their discovery in all three domains of life further suggests the possibility that they were present at the time of the last universal common ancestor (LUCA).Significance StatementThis work establishes that amyloid-forming, prion-like domains exist in Archaea and are capable of vertically transmitting their prion phenotype – allowing them to function as protein-based elements of inheritance. These observations, coupled with prior discoveries in Eukarya and Bacteria, suggest that prion-based self-assembly was likely present in life’s last universal common ancestor (LUCA), and therefore may be one of the most ancient epigenetic mechanisms.

In vitro and in vivo polysaccharides assembly: ultrastructural and cytochemical study of growing plant cell wall components.

1978 ◽  
Vol 36 (2) ◽  
pp. 434-435
Author(s):  
D. Reis ◽  
B. Vian ◽  
J. C. Roland
Keyword(s):  
Cell Wall ◽  
Self Assembly ◽  
Plant Cell Wall ◽  
Higher Plants ◽  
Three Dimensional ◽  
Cytochemical Study ◽  
Wall Components

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.

The Nature of Rapidly Extracted Phycocyanin from the Blue-Green Alga Plectonema Boryanum

1971 ◽  
Vol 29 ◽  
pp. 366-367
Author(s):  
M. Kessel ◽  
R. MacColl
Keyword(s):  
Self Assembly ◽  
Analytical Ultracentrifugation ◽  
Uranyl Acetate ◽  
The Self ◽  
Major Protein ◽  
Subunit Structure ◽  
Blue Green Alga ◽  
Thin Sections ◽  
Blue Green Algae ◽  
Cacodylate Buffer

The major protein of the blue-green algae is the biliprotein, C-phycocyanin (Amax = 620 nm), which is presumed to exist in the cell in the form of distinct aggregates called phycobilisomes. The self-assembly of C-phycocyanin from monomer to hexamer has been extensively studied, but the proposed next step in the assembly of a phycobilisome, the formation of 19s subunits, is completely unknown. We have used electron microscopy and analytical ultracentrifugation in combination with a method for rapid and gentle extraction of phycocyanin to study its subunit structure and assembly.To establish the existence of phycobilisomes, cells of P. boryanum in the log phase of growth, growing at a light intensity of 200 foot candles, were fixed in 2% glutaraldehyde in 0.1M cacodylate buffer, pH 7.0, for 3 hours at 4°C. The cells were post-fixed in 1% OsO4 in the same buffer overnight. Material was stained for 1 hour in uranyl acetate (1%), dehydrated and embedded in araldite and examined in thin sections.

Video real-time imaging of artificial membranes during freeze-drying by cryo-electron microscopy

1988 ◽  
Vol 46 ◽  
pp. 16-17
Author(s):  
Alan S. Rudolph ◽  
Ronald R. Price
Keyword(s):  
Real Time ◽  
Self Assembly ◽  
Freeze Drying ◽  
Video Capture ◽  
Drying Process ◽  
Artificial Membranes ◽  
The Past ◽  
Cryo Electron Microscopy ◽  
Spherical Structures ◽  
Capture Techniques

We have employed cryoelectron microscopy to visualize events that occur during the freeze-drying of artificial membranes by employing real time video capture techniques. Artificial membranes or liposomes which are spherical structures within internal aqueous space are stabilized by water which provides the driving force for spontaneous self-assembly of these structures. Previous assays of damage to these structures which are induced by freeze drying reveal that the two principal deleterious events that occur are 1) fusion of liposomes and 2) leakage of contents trapped within the liposome [1]. In the past the only way to access these events was to examine the liposomes following the dehydration event. This technique allows the event to be monitored in real time as the liposomes destabilize and as water is sublimed at cryo temperatures in the vacuum of the microscope. The method by which liposomes are compromised by freeze-drying are largely unknown. This technique has shown that cryo-protectants such as glycerol and carbohydrates are able to maintain liposomal structure throughout the drying process.

Biomimetic materials: An introduction

1992 ◽  
Vol 50 (2) ◽  
pp. 1020-1021 ◽  
Author(s):  
M. Sarikaya ◽  
J. T. Staley ◽  
I. A. Aksay
Keyword(s):  
Self Assembly ◽  
Structural Control ◽  
Hierarchical Structures ◽  
Ceramic Composites ◽  
Advanced Materials ◽  
Length Scale ◽  
Spider Webs ◽  
Biomimetic Materials ◽  
Synthetic Materials ◽  
All Ceramic

Biomimetics is an area of research in which the analysis of structures and functions of natural materials provide a source of inspiration for design and processing concepts for novel synthetic materials. Through biomimetics, it may be possible to establish structural control on a continuous length scale, resulting in superior structures able to withstand the requirements placed upon advanced materials. It is well recognized that biological systems efficiently produce complex and hierarchical structures on the molecular, micrometer, and macro scales with unique properties, and with greater structural control than is possible with synthetic materials. The dynamism of these systems allows the collection and transport of constituents; the nucleation, configuration, and growth of new structures by self-assembly; and the repair and replacement of old and damaged components. These materials include all-organic components such as spider webs and insect cuticles (Fig. 1); inorganic-organic composites, such as seashells (Fig. 2) and bones; all-ceramic composites, such as sea urchin teeth, spines, and other skeletal units (Fig. 3); and inorganic ultrafine magnetic and semiconducting particles produced by bacteria and algae, respectively (Fig. 4).

Interrelationship of the cellular distribution and secretion of regular structure (RS) protein in Bacillus licheniformis nm 105

1992 ◽  
Vol 50 (1) ◽  
pp. 712-713
Author(s):  
Xiaorong Zhu ◽  
Richard McVeigh ◽  
Bijan K. Ghosh
Keyword(s):  
Alkaline Phosphatase ◽  
Bacillus Licheniformis ◽  
Self Assembly ◽  
Gel Electrophoresis ◽  
Culture Supernatant ◽  
Regular Structure ◽  
The Self ◽  
Cellular Distribution ◽  
Structural Protein ◽  
Laboratory Cultures

A mutant of Bacillus licheniformis 749/C, NM 105 exhibits some notable properties, e.g., arrest of alkaline phosphatase secretion and overexpression and hypersecretion of RS protein. Although RS is known to be widely distributed in many microbes, it is rarely found, with a few exceptions, in laboratory cultures of microorganisms. RS protein is a structural protein and has the unusual properties to form aggregate. This characteristic may have been responsible for the self assembly of RS into regular tetragonal structures. Another uncommon characteristic of RS is that enhanced synthesis and secretion which occurs when the cells cease to grow. Assembled RS protein with a tetragonal structure is not seen inside cells at any stage of cell growth including cells in the stationary phase of growth. Gel electrophoresis of the culture supernatant shows a very large amount of RS protein in the stationary culture of the B. licheniformis. It seems, Therefore, that the RS protein is cotranslationally secreted and self assembled on the envelope surface.

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