Faculty Opinions recommendation of Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains.

2020 ◽  
Author(s):  
Mingjie Zhang
Keyword(s):  
Posttranslational Modifications ◽  
Structural Diversity

scholarly journals Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains

Cell ◽  
2020 ◽  
Vol 180 (4) ◽  
pp. 633-644.e12 ◽  
Author(s):  
Tamta Arakhamia ◽  
Christina E. Lee ◽  
Yari Carlomagno ◽  
Duc M. Duong ◽  
Sean R. Kundinger ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Structural Diversity

scholarly journals A microtubule bestiary: structural diversity in tubulin polymers

2017 ◽  
Vol 28 (22) ◽  
pp. 2924-2931 ◽  
Author(s):  
Sami Chaaban ◽  
Gary J. Brouhard
Keyword(s):  
Posttranslational Modifications ◽  
Functional Significance ◽  
Structural Diversity ◽  
Higher Order ◽  
Eukaryotic Cells ◽  
Tubulin Isoforms ◽  
Standing Question ◽  
Microtubule Structure

Microtubules are long, slender polymers of αβ-tubulin found in all eukaryotic cells. Tubulins associate longitudinally to form protofilaments, and adjacent protofilaments associate laterally to form the microtubule. In the textbook view, microtubules are 1) composed of 13 protofilaments, 2) arranged in a radial array by the centrosome, and 3) built into the 9+2 axoneme. Although these canonical structures predominate in eukaryotes, microtubules with divergent protofilament numbers and higher-order microtubule assemblies have been discovered throughout the last century. Here we survey these noncanonical structures, from the 4-protofilament microtubules of Prosthecobacter to the 40-protofilament accessory microtubules of mantidfly sperm. We review the variety of protofilament numbers observed in different species, in different cells within the same species, and in different stages within the same cell. We describe the determinants of protofilament number, namely nucleation factors, tubulin isoforms, and posttranslational modifications. Finally, we speculate on the functional significance of these diverse polymers. Equipped with novel tubulin-purification tools, the field is now prepared to tackle the long-standing question of the evolutionary basis of microtubule structure.

scholarly journals From Posttranslational Modifications to Disease Phenotype: A Substrate Selection Hypothesis in Neurodegenerative Diseases

2021 ◽  
Vol 22 (2) ◽  
pp. 901
Author(s):  
Ilia V. Baskakov
Keyword(s):  
Neurodegenerative Diseases ◽  
Posttranslational Modifications ◽  
Structural Diversity ◽  
Protein Isoforms ◽  
Causative Role ◽  
Substrate Selection ◽  
Cell Region ◽  
Selection Hypothesis ◽  
Clinical Phenotypes ◽  
Disease Phenotypes

A number of neurodegenerative diseases including prion diseases, tauopathies and synucleinopathies exhibit multiple clinical phenotypes. A diversity of clinical phenotypes has been attributed to the ability of amyloidogenic proteins associated with a particular disease to acquire multiple, conformationally distinct, self-replicating states referred to as strains. Structural diversity of strains formed by tau, α-synuclein or prion proteins has been well documented. However, the question how different strains formed by the same protein elicit different clinical phenotypes remains poorly understood. The current article reviews emerging evidence suggesting that posttranslational modifications are important players in defining strain-specific structures and disease phenotypes. This article put forward a new hypothesis referred to as substrate selection hypothesis, according to which individual strains selectively recruit protein isoforms with a subset of posttranslational modifications that fit into strain-specific structures. Moreover, it is proposed that as a result of selective recruitment, strain-specific patterns of posttranslational modifications are formed, giving rise to unique disease phenotypes. Future studies should define whether cell-, region- and age-specific differences in metabolism of posttranslational modifications play a causative role in dictating strain identity and structural diversity of strains of sporadic origin.

scholarly journals Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains

Cell ◽  
2021 ◽  
Vol 184 (25) ◽  
pp. 6207-6210
Author(s):  
Tamta Arakhamia ◽  
Christina E. Lee ◽  
Yari Carlomagno ◽  
Mukesh Kumar ◽  
Duc M. Duong ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Structural Diversity

scholarly journals Linear Peptides—A Combinatorial Innovation in the Venom of Some Modern Spiders

2021 ◽  
Vol 8 ◽  
Author(s):  
Lucia Kuhn-Nentwig ◽  
Heidi E. L. Lischer ◽  
Stano Pekár ◽  
Nicolas Langenegger ◽  
Maria J. Albo ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Amino Acid Level ◽  
Structural Diversity ◽  
Venom Gland ◽  
Fast Method ◽  
Spider Species ◽  
Linear Peptide ◽  
Complex Precursor ◽  
Generation Sequencing ◽  
Active Substances

In the venom of spiders, linear peptides (LPs), also called cytolytical or antimicrobial peptides, represent a largely neglected group of mostly membrane active substances that contribute in some spider species considerably to the killing power of spider venom. By next-generation sequencing venom gland transcriptome analysis, we investigated 48 spider species from 23 spider families and detected LPs in 20 species, belonging to five spider families (Ctenidae, Lycosidae, Oxyopidae, Pisauridae, and Zodariidae). The structural diversity is extraordinary high in some species: the lynx spider Oxyopes heterophthalmus contains 62 and the lycosid Pardosa palustris 60 different LPs. In total, we identified 524 linear peptide structures and some of them are in lycosids identical on amino acid level. LPs are mainly encoded in complex precursor structures in which, after the signal peptide and propeptide, 13 or more LPs (Hogna radiata) are connected by linkers. Besides Cupiennius species, also in Oxyopidae, posttranslational modifications of some precursor structures result in the formation of two-chain peptides. It is obvious that complex precursor structures represent a very suitable and fast method to produce a high number and a high diversity of bioactive LPs as economically as possible. At least in Lycosidae, Oxyopidae, and in the genus Cupiennius, LPs reach very high Transcripts Per Kilobase Million values, indicating functional importance within the envenomation process.

In the Pursuit of (Ald)Imine Surrogates for the Direct Asymmetric Synthesis of Non-Proteinogenic α-Amino Acids

Synthesis ◽  
2021 ◽  
Author(s):  
Stéphane P. Roche
Keyword(s):  
Amino Acids ◽  
Asymmetric Synthesis ◽  
Nucleophilic Substitution ◽  
Posttranslational Modifications ◽  
Kinetic Studies ◽  
Structural Diversity ◽  
Building Blocks ◽  
Bioactive Molecules ◽  
Biological Functions ◽  
Imino Esters

Nature remarkably employs posttranslational modifications of the 20 canonical α-amino acids to devise a far larger structural, conformational, and functional diversity found in non-proteinogenic amino acids (NPAAs) which ultimately translates into a plethora of complex biological functions. Synthetic chemists are continuously trying to reproduce and even extrapolate the repertoire of NPAA building blocks to build structural diversity into bioactive molecules and materials. The direct asymmetric functionalization of α-imino esters represents one of the most robust and attractive routes to NPAAs. This review summarizes the most prominent examples of bench-stable (ald)imine surrogates exploited for the synthesis of NPAAs including our most recent results in the nucleophilic substitution of α-haloglycines and other α-haloaminals. A synopsis of kinetic studies, reaction optimizations, and enantioselective catalytic methods is also presented.

Neurofilaments and Paired Helical Filaments

1985 ◽  
Vol 43 ◽  
pp. 740-743
Author(s):  
J. Metuzals
Keyword(s):  
Animal Model ◽  
Posttranslational Modifications ◽  
Posttranslational Modification ◽  
Giant Axon ◽  
Paired Helical Filaments ◽  
Squid Giant Axon ◽  
In Vitro Experiments ◽  
Thin Sections ◽  
Structural Relationships

It has been demonstrated that the neurofibrillary tangles in biopsies of Alzheimer patients, composed of typical paired helical filaments (PHF), consist also of typical neurofilaments (NF) and 15nm wide filaments. Close structural relationships, and even continuity between NF and PHF, have been observed. In this paper, such relationships are investigated from the standpoint that the PHF are formed through posttranslational modifications of NF. To investigate the validity of the posttranslational modification hypothesis of PHF formation, we have identified in thin sections from frontal lobe biopsies of Alzheimer patients all existing conformations of NF and PHF and ordered these conformations in a hypothetical sequence. However, only experiments with animal model preparations will prove or disprove the validity of the interpretations of static structural observations made on patients. For this purpose, the results of in vitro experiments with the squid giant axon preparations are compared with those obtained from human patients. This approach is essential in discovering etiological factors of Alzheimer's disease and its early diagnosis.

Posttranslational Modifications of Ribosomal Proteins in Escherichia coli

Acta Naturae ◽  
2011 ◽  
Vol 3 (2) ◽  
pp. 22-33 ◽  
Author(s):  
M V Nesterchuk ◽  
P V Sergiev ◽  
O A Dontsova
Keyword(s):  
Escherichia Coli ◽  
Posttranslational Modifications ◽  
Ribosomal Proteins

Metal-, and Organocatalyst-Free One-Pot Assembly of Chiral Aza-Tricyclic Molecules: Creating Six Contiguous Stereocenters from 2-D-Structures and an Amino Acid

2020 ◽  
Author(s):  
Dung Do
Keyword(s):  
Amino Acid ◽  
Chemical Space ◽  
Structural Diversity ◽  
Therapeutic Agents ◽  
Chiral Molecules ◽  
One Pot ◽  
Complex Molecules ◽  
Chiral Catalyst ◽  
Chiral Complex ◽  
Free Process

<p>Chiral molecules with their defined 3-D structures are of paramount importance for the study of chemical biology and drug discovery. Having rich structural diversity and unique stereoisomerism, chiral molecules offer a large chemical space that can be explored for the design of new therapeutic agents.<sup>1</sup> Practically, chiral architectures are usually prepared from organometallic and organocatalytic processes where a transition metal or an organocatalyst is tailor-made for desired reactions. As a result, developing a method that enables rapid assembly of chiral complex molecules under metal- and organocatalyst-free condition represents a daunting challenge. Here we developed a straightforward route to create a chiral 3-D structure from 2-D structures and an amino acid without any chiral catalyst. The center of this research is the design of a <a>special chiral spiroimidazolidinone cyclohexadienone intermediate</a>, a merger of a chiral reactive substrate with multiple nucleophillic/electrophillic sites and a transient organocatalyst. <a>This unique substrate-catalyst (“subcatalyst”) dual role of the intermediate enhances </a><a>the coordinational proximity of the chiral substrate and catalyst</a> in the key Aza-Michael/Michael cascade resulting in a substantial steric discrimination and an excellent overall diastereoselectivity. Whereas the “subcatalyst” (hidden catalyst) is not present in the reaction’s initial components, which renders a chiral catalyst-free process, it is strategically produced to promote sequential self-catalyzed reactions. The success of this methodology will pave the way for many efficient preparations of chiral complex molecules and aid for the quest to create next generation of therapeutic agents.</p>

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