scholarly journals Deimination and Peptidylarginine Deiminases in Skin Physiology and Diseases

2020 ◽  
Vol 21 (2) ◽  
pp. 566 ◽  
Author(s):  
Marie-Claire Méchin ◽  
Hidenari Takahara ◽  
Michel Simon
Keyword(s):  
Amino Acid ◽  
Skin Diseases ◽  
African Ancestry ◽  
Hair Shaft ◽  
Hair Follicles ◽  
Peptide Sequence ◽  
Keratinocyte Differentiation ◽  
Post Translational Modification ◽  
Calcium Dependent ◽  
Skin Physiology

Deimination, also known as citrullination, corresponds to the conversion of the amino acid arginine, within a peptide sequence, into the non-standard amino acid citrulline. This post-translational modification is catalyzed by a family of calcium-dependent enzymes called peptidylarginine deiminases (PADs). Deimination is implicated in a growing number of physiological processes (innate and adaptive immunity, gene regulation, embryonic development, etc.) and concerns several human diseases (rheumatoid arthritis, neurodegenerative diseases, female infertility, cancer, etc.). Here, we update the involvement of PADs in both the homeostasis of skin and skin diseases. We particularly focus on keratinocyte differentiation and the epidermal barrier function, and on hair follicles. Indeed, alteration of PAD activity in the hair shaft is responsible for two hair disorders, the uncombable hair syndrome and a particular form of inflammatory scarring alopecia, mainly affecting women of African ancestry.

scholarly journals Why Pashmina Goat Produces Long Hair-fiber and Barbari doesn’t: A Differential Gene Expression Study

2021 ◽  
Author(s):  
Rashid Saif ◽  
Tania Mahmood ◽  
Aniqa Ejaz ◽  
Saeeda Zia
Keyword(s):  
Gene Expression ◽  
Differential Gene Expression ◽  
Transcriptome Assembly ◽  
Hair Shaft ◽  
Hair Follicles ◽  
Differentially Expressed ◽  
Keratinocyte Differentiation ◽  
Dermal Papilla Cells ◽  
Differential Gene ◽  
Hair Fiber

The Pashmina and Barbari are two famous goat breeds found in the wide areas of the Indo-Pak region. Pashmina is famous for its long hair-fiber (Cashmere) production while Barbari is not-selected for this trait. So, the mRNA expression profiling in the skin samples of both breeds would be an attractive and judicious approach for detecting putative genes involved in this valued trait. Here, we performed differential gene expression analysis on publicly available RNA-Seq data from both breeds. Out of 44,617,994 filtered reads of Pashmina and 55,995,999 of Barbari which are 76.48% and 73.69% mapped to the ARS1 reference transcriptome assembly respectively. A pairwise comparison of both breeds resulted in 47,159 normalized expressed transcripts while 8,414 transcripts are differentially expressed above the significant threshold. Among these, 4,788 are upregulated in Pashmina while 3,626 transcripts are upregulated in Barbari. Fifty-nine transcripts harbor 57 genes including 32 LOC genes and 24 are annotated genes which were selected on the basis of TMM counts > 500. Genes with ectopic expressions other than uncharacterized and LOC symbol genes are Keratins (KRT) and Keratin Associated Proteins (KRTAPs), CystatinA&6, TCHH, SPRR4, PPIA, SLC25A4, S100A11, DMKN, LOR, ANXA2, PRR9 and SFN. All of these genes are likely to be involved in keratinocyte differentiation, sulfur matrix proteins, dermal papilla cells, hair follicles proliferation, hair curvature, wool fiber diameter, hair transition, hair shaft differentiation and its keratinization. These differentially expressed reported genes are critically valuable for enhancing the quality and quantity of the pashmina fiber and overall breed improvement. This study will also provide important information on hair follicle differentiation for further enrichment analyses and introducing this valued trait to other goat breeds as well.

Molecular analysis of a cytoplasmic dynein light intermediate chain reveals homology to a family of ATPases

1995 ◽  
Vol 108 (1) ◽  
pp. 17-24 ◽  
Author(s):  
S.M. Hughes ◽  
K.T. Vaughan ◽  
J.S. Herskovits ◽  
R.B. Vallee
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Cytoplasmic Dynein ◽  
Peptide Sequence ◽  
Organelle Transport ◽  
Cdna Clones ◽  
Post Translational Modification ◽  
Sequence Element ◽  
Transporter Family ◽  
Intermediate Chains

Cytoplasmic dynein is a multi-subunit complex involved in retrograde organelle transport and some aspects of mitosis. In previous work we have cloned and sequenced cDNAs encoding the rat cytoplasmic dynein heavy and intermediate chains. Here we report the cloning of the remaining class of cytoplasmic dynein subunits, which we refer to as the light intermediate chains (LICs: 53–59 kDa). Four LIC electrophoretic bands were resolved in purified bovine cytoplasmic dynein preparations by one-dimensional gel electrophoresis. These four bands were simplified to two bands (LIC53/55 and LIC57/59) by alkaline phosphatase treatment. N-terminal amino acid sequence was obtained from a total of 11 proteolytic peptides generated from both LIC53/55 and LIC57/59. Overlapping cDNA clones encoding LIC53/55 were isolated by oligonucleotide screening using probes based on the LIC53/55 peptide sequence. The cDNA sequence contained a 497 codon open reading frame encoding a polypeptide with a molecular mass of approximately 55 kDa. Each of the LIC53/55 peptides was found within the deduced amino acid sequence, as well as four of the LIC57/59 peptides. Analysis of the LIC53/55 primary sequence revealed homology with the ABC transporter family of ATPases in the region surrounding the P-loop sequence element. Together these data identify the LICs as a novel family of dynein subunits with potential ATPase activity. They also reveal that the complexity of the LICs is due to both post-translational modification and the existence of at least two LIC polypeptides for which we propose the names LIC-1a and LIC-2.

scholarly journals iAmideV-Deep: Valine Amidation Site Prediction in Proteins Using Deep Learning and Pseudo Amino Acid Compositions

Symmetry ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 560
Author(s):  
Sheraz Naseer ◽  
Rao Faizan Ali ◽  
Amgad Muneer ◽  
Suliman Mohamed Fati
Keyword(s):  
Amino Acid ◽  
Computational Models ◽  
Ex Vivo ◽  
Biologically Active ◽  
Peptide Sequence ◽  
Post Translational Modification ◽  
Amino Acid Compositions ◽  
Efficient Alternative

Amidation is an important post translational modification where a peptide ends with an amide group (–NH2) rather than carboxyl group (–COOH). These amidated peptides are less sensitive to proteolytic degradation with extended half-life in the bloodstream. Amides are used in different industries like pharmaceuticals, natural products, and biologically active compounds. The in-vivo, ex-vivo, and in-vitro identification of amidation sites is a costly and time-consuming but important task to study the physiochemical properties of amidated peptides. A less costly and efficient alternative is to supplement wet lab experiments with accurate computational models. Hence, an urgent need exists for efficient and accurate computational models to easily identify amidated sites in peptides. In this study, we present a new predictor, based on deep neural networks (DNN) and Pseudo Amino Acid Compositions (PseAAC), to learn efficient, task-specific, and effective representations for valine amidation site identification. Well-known DNN architectures are used in this contribution to learn peptide sequence representations and classify peptide chains. Of all the different DNN based predictors developed in this study, Convolutional neural network-based model showed the best performance surpassing all other DNN based models and reported literature contributions. The proposed model will supplement in-vivo methods and help scientists to determine valine amidation very efficiently and accurately, which in turn will enhance understanding of the valine amidation in different biological processes.

scholarly journals Non-invasive human skin transcriptome analysis using mRNA in skin surface lipids

2021 ◽  
Author(s):  
Takayoshi Inoue ◽  
Tetsuya Kuwano ◽  
Yuya Uehara ◽  
Michiko Yano ◽  
Naoki Oya ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Transcriptome Analysis ◽  
Skin Diseases ◽  
Skin Surface ◽  
Hair Follicles ◽  
Sebaceous Glands ◽  
Non Invasive ◽  
Skin Physiology ◽  
Surface Lipids ◽  
Skin Surface Lipids

Non-invasive acquisition of mRNA data from the skin would be extremely useful for understanding skin physiology and diseases. Inspired by the holocrine process, in which the sebaceous glands secrete cell contents into the sebum, we focused on the possible presence of mRNAs in skin surface lipids (SSLs). We found that measurable human mRNAs exist in SSLs, where sebum protects them from degradation by RNases. The AmpliSeq transcriptome analysis was modified to measure SSL-RNAs, and our results revealed that SSL-RNAs predominantly contained mRNAs derived from sebaceous glands, epidermis, and hair follicles. Analysis of SSL-RNAs non-invasively collected from patients with atopic dermatitis revealed significantly increased expression of inflammation-related genes and decreased expression of terminal differentiation-related genes, consistent with the results of previous reports. Further, we found that lipid synthesis-related genes were downregulated in the sebaceous glands of patients with atopic dermatitis. These results indicate that the analysis of SSL-RNAs is promising to understand the pathophysiology of skin diseases.

Mislocalization of Adherens Junction- Associated Proteins in a Patient with Darier Disease

2018 ◽  
Vol 2 (3) ◽  
pp. 184-201
Author(s):  
George D Glinos ◽  
Irena Pastar ◽  
Marjana Tomic-Canic ◽  
Rivka C Stone
Keyword(s):  
Adherens Junction ◽  
Cellular Adhesion ◽  
Calcium Flux ◽  
Keratinocyte Differentiation ◽  
Calcium Dependent ◽  
Endoplasmic Reticulum Calcium ◽  
Darier Disease ◽  
Associated Proteins ◽  
Attachment Proteins ◽  
E Cadherin

Darier disease (DD) is an autosomal dominant keratinizing genodermatosis that manifests clinically with red-brown pruritic papules in a seborrheic distribution often in association with palmoplantar pits and dystrophic nail changes. It is caused by mutation in ATP2A2 which encodes a sarco/endoplasmic reticulum calcium ATPase isoform 2 (SERCA2) pump that regulates calcium flux. Consequent alteration of intracellular calcium homeostasis is thought to impair trafficking of cellular adhesion proteins and to lead to aberrant keratinocyte differentiation, contributing to the characteristic histopathologic features of acantholysis and dyskeratosis in DD, though the precise mechanisms are incompletely understood. Previous studies have identified defective localization of desmosomal attachment proteins in skin biopsies and cultured keratinocytes from DD patients, but reports of effects on adherens junction proteins (including calcium-dependent E-cadherin) are conflicting. Here we describe a case of DD presenting with characteristic clinical and histologic features in which we performed immunofluorescence staining of four adherens junction-associated proteins (E-cadherin, α-catenin, β-catenin, and vinculin). In lesional (acantholytic) DD skin, we identified loss of distinctive bright membranous staining that was present at the periphery of keratinocytes throughout the epidermis in the healthy skin of a matched donor. Perilesional (non-acantholytic) portions of DD skin partially recapitulated the normal phenotype. Our findings support a role for SERCA2 dysfunction in impaired assembly of adherens junctions, which together with defective desmosomes contribute to acantholysis in DD.

scholarly journals CirBiTree: Citrullination Site Inference Based on a Fuzzy Neural Network and Flexible Neural Tree

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Chuandong Song ◽  
Haifeng Wang
Keyword(s):  
Neural Network ◽  
Fuzzy Neural Network ◽  
Classification Model ◽  
Peptide Sequence ◽  
Sequence Information ◽  
Post Translational Modification ◽  
Fuzzy Neural ◽  
Human Complex ◽  
Better Than

Emerging evidence demonstrates that post-translational modification plays an important role in several human complex diseases. Nevertheless, considering the inherent high cost and time consumption of classical and typical in vitro experiments, an increasing attention has been paid to the development of efficient and available computational tools to identify the potential modification sites in the level of protein. In this work, we propose a machine learning-based model called CirBiTree for identification the potential citrullination sites. More specifically, we initially utilize the biprofile Bayesian to extract peptide sequence information. Then, a flexible neural tree and fuzzy neural network are employed as the classification model. Finally, the most available length of identified peptides has been selected in this model. To evaluate the performance of the proposed methods, some state-of-the-art methods have been employed for comparison. The experimental results demonstrate that the proposed method is better than other methods. CirBiTree can achieve 83.07% in sn%, 80.50% in sp, 0.8201 in F1, and 0.6359 in MCC, respectively.

scholarly journals Post translational modifications of milk proteins in geographically diverse goat breeds

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
P. K. Rout ◽  
M. Verma
Keyword(s):  
Protein Function ◽  
Whey Proteins ◽  
Milk Proteins ◽  
Goat Milk ◽  
Peptide Sequence ◽  
Cow Milk ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Functional Roles ◽  
Dpp Iv

AbstractGoat milk is a source of nutrition in difficult areas and has lesser allerginicity than cow milk. It is leading in the area for nutraceutical formulation and drug development using goat mammary gland as a bioreactor. Post translational modifications of a protein regulate protein function, biological activity, stabilization and interactions. The protein variants of goat milk from 10 breeds were studied for the post translational modifications by combining highly sensitive 2DE and Q-Exactive LC-MS/MS. Here we observed high levels of post translational modifications in 201 peptides of 120 goat milk proteins. The phosphosites observed for CSN2, CSN1S1, CSN1S2, CSN3 were 11P, 13P, 17P and 6P, respectively in 105 casein phosphopeptides. Whey proteins BLG and LALBA showed 19 and 4 phosphosites respectively. Post translational modification was observed in 45 low abundant non-casein milk proteins mainly associated with signal transduction, immune system, developmental biology and metabolism pathways. Pasp is reported for the first time in 47 sites. The rare conserved peptide sequence of (SSSEE) was observed in αS1 and αS2 casein. The functional roles of identified phosphopeptides included anti-microbial, DPP-IV inhibitory, anti-inflammatory and ACE inhibitory. This is first report from tropics, investigating post translational modifications in casein and non-casein goat milk proteins and studies their interactions.

scholarly journals Deimination, Intermediate Filaments and Associated Proteins

2020 ◽  
Vol 21 (22) ◽  
pp. 8746
Author(s):  
Julie Briot ◽  
Michel Simon ◽  
Marie-Claire Méchin
Keyword(s):  
Rheumatoid Arthritis ◽  
Multiple Sclerosis ◽  
Cell Differentiation ◽  
Intermediate Filaments ◽  
Cross Linking ◽  
Post Translational Modification ◽  
Innate And Adaptive Immunity ◽  
Calcium Dependent ◽  
Physiological Processes ◽  
Associated Proteins

Deimination (or citrullination) is a post-translational modification catalyzed by a calcium-dependent enzyme family of five peptidylarginine deiminases (PADs). Deimination is involved in physiological processes (cell differentiation, embryogenesis, innate and adaptive immunity, etc.) and in autoimmune diseases (rheumatoid arthritis, multiple sclerosis and lupus), cancers and neurodegenerative diseases. Intermediate filaments (IF) and associated proteins (IFAP) are major substrates of PADs. Here, we focus on the effects of deimination on the polymerization and solubility properties of IF proteins and on the proteolysis and cross-linking of IFAP, to finally expose some features of interest and some limitations of citrullinomes.

scholarly journals Amino acid sequence of the penicillin-binding protein/dd-peptidase of Streptomyces K15. Predicted secondary structures of the low Mr penicillin-binding proteins of class A

1991 ◽  
Vol 279 (1) ◽  
pp. 223-230 ◽  
Author(s):  
P Palomeque-Messia ◽  
S Englebert ◽  
M Leyh-Bouille ◽  
M Nguyen-Distèche ◽  
C Duez ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Residue ◽  
Active Sites ◽  
Binding Protein ◽  
Secondary Structures ◽  
Peptide Sequence ◽  
Penicillin Binding Protein ◽  
Signal Peptide Sequence ◽  
Beta Lactamases ◽  
Class A

The low-Mr penicillin-binding protein (PBP)/DD-transpeptidase of Streptomyces K15 is synthesized in the form of a 291-amino acid-residue precursor possessing a cleavable 29-amino acid-residue signal peptide. Sequence-similarity searches and hydrophobic-cluster analysis show that the Streptomyces K15 enzyme, the Escherichia coli PBPs/DD-carboxy-peptidases 5 and 6, the Bacillus subtilis PBP/DD-carboxypeptidase 5 and the spoIIA product (a putative PBP involved in the sporulation of B. subtilis) are structurally related and form a distinct class A of low-Mr PBPs/DD-peptidases. The distribution of the hydrophobic clusters along the amino acid sequences also shows that the Streptomyces K15 PBP, and by extension the other PBPs of class A, have similarity in the polypeptide folding, with the beta-lactamases of class A, with as reference the Streptomyces albus G and Staphylococcus aureus beta-lactamases of known three-dimensional structure. This comparison allows one to predict most of the secondary structures in the PBPs and the amino acid motifs that define the enzyme active sites.

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