scholarly journals Molecular characterization of myelin basic protein a (mbpa) gene from red-bellied pacu (Piaractus brachypomus)

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Juan Sebastian Cruz-Méndez ◽  
María Paula Herrera-Sánchez ◽  
Ángel Enrique Céspedes-Rubio ◽  
Iang Schroniltgen Rondón-Barragán
Keyword(s):  
Gene Expression ◽  
Brain Injury ◽  
Myelin Basic Protein ◽  
Molecular Characterization ◽  
Basic Protein ◽  
Protein A ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Disordered Regions

Abstract Background Myelin basic protein (MBP) is one of the most important structural components of the myelin sheaths in both central and peripheral nervous systems. MBP has several functions including organization of the myelin membranes, reorganization of the cytoskeleton during the myelination process, and interaction with the SH3 domain in signaling pathways. Likewise, MBP has been proposed as a marker of demyelination in traumatic brain injury and chemical exposure. Methods The aim of this study was to molecularly characterize the myelin basic protein a (mbpa) gene from the Colombian native fish, red-bellied pacu, Piaractus brachypomus. Bioinformatic tools were used to identify the phylogenetic relationships, physicochemical characteristics, exons, intrinsically disordered regions, and conserved domains of the protein. Gene expression was assessed by qPCR in three models corresponding to sublethal chlorpyrifos exposure, acute brain injury, and anesthesia experiments. Results mbpa complete open reading frame was identified with 414 nucleotides distributed in 7 exons that encode 137 amino acids. MBPa was recognized as belonging to the myelin basic protein family, closely related with orthologous proteins, and two intrinsically disordered regions were established within the sequence. Gene expression of mbpa was upregulated in the optic chiasm of the chlorpyrifos exposed fish in contrast to the control group. Conclusions The physicochemical computed features agree with the biological functions of MBP, and basal gene expression was according to the anatomical distribution in the tissues analyzed. This study is the first molecular characterization of mbpa from the native species Piaractus brachypomus.

scholarly journals Discovering molecular features of intrinsically disordered regions by using evolution for contrastive learning

2021 ◽  
Author(s):  
Alex X Lu ◽  
Amy X Lu ◽  
Iva Pritisanac ◽  
Taraneh Zarin ◽  
Julie D Forman-Kay ◽  
...  
Keyword(s):  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Molecular Features ◽  
The Neural Network ◽  
Amino Acid Repeats ◽  
Functional Features ◽  
Feature Discovery ◽  
Discovery Method ◽  
Disordered Regions

A major challenge to the characterization of intrinsically disordered regions (IDRs), which are widespread in the proteome, but relatively poorly understood, is the identification of molecular features, such as short motifs, amino acid repeats and physicochemical properties that mediate the functions of these regions. Here, we introduce a proteome-scale feature discovery method for IDRs. Our method, which we call "reverse homology", exploits the principle that important functional features are conserved over evolution as a contrastive learning signal for deep learning: given a set of homologous IDRs, the neural network has to correctly choose a randomly held-out homologue from another set of IDRs sampled randomly from the proteome. We pair reverse homology with a simple architecture and interpretation techniques, and show that the network learns conserved features of IDRs that can be interpreted as motifs, repeats, and other features. We also show that our model can be used to produce specific predictions of what residues and regions are most important to the function, providing a computational strategy for designing mutagenesis experiments in uncharacterized IDRs. Our results suggest that feature discovery using neural networks is a promising avenue to gain systematic insight into poorly understood protein sequences.

scholarly journals Analysis of the Mechanism by Which Glucose Inhibits Maltose Induction of MAL Gene Expression in Saccharomyces

Genetics ◽  
2000 ◽  
Vol 154 (1) ◽  
pp. 121-132
Author(s):  
Zhen Hu ◽  
Yingzi Yue ◽  
Hua Jiang ◽  
Bin Zhang ◽  
Peter W Sherwood ◽  
...  
Keyword(s):  
Gene Expression ◽  
Glucose Repression ◽  
Protein A ◽  
The Other ◽  
Maltose Permease ◽  
Inducer Exclusion ◽  
Glucose Inhibition ◽  
Independent Mechanism ◽  
Mal Genes

Abstract Expression of the MAL genes required for maltose fermentation in Saccharomyces cerevisiae is induced by maltose and repressed by glucose. Maltose-inducible regulation requires maltose permease and the MAL-activator protein, a DNA-binding transcription factor encoded by MAL63 and its homologues at the other MAL loci. Previously, we showed that the Mig1 repressor mediates glucose repression of MAL gene expression. Glucose also blocks MAL-activator-mediated maltose induction through a Mig1p-independent mechanism that we refer to as glucose inhibition. Here we report the characterization of this process. Our results indicate that glucose inhibition is also Mig2p independent. Moreover, we show that neither overexpression of the MAL-activator nor elimination of inducer exclusion is sufficient to relieve glucose inhibition, suggesting that glucose acts to inhibit induction by affecting maltose sensing and/or signaling. The glucose inhibition pathway requires HXK2, REG1, and GSF1 and appears to overlap upstream with the glucose repression pathway. The likely target of glucose inhibition is Snf1 protein kinase. Evidence is presented indicating that, in addition to its role in the inactivation of Mig1p, Snf1p is required post-transcriptionally for the synthesis of maltose permease whose function is essential for maltose induction.

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