scholarly journals Conformational and Spectroscopic Characterization of Intrinsically Disordered Regions in Proteins

2011 ◽  
Vol 100 (3) ◽  
pp. 13a
Author(s):  
Anurag Sethi ◽  
Dung Vu ◽  
S. Gnanakaran
Keyword(s):  
Spectroscopic Characterization ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Disordered Regions

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 Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Vikas A. Tillu ◽  
James Rae ◽  
Ya Gao ◽  
Nicholas Ariotti ◽  
Matthias Floetenmeyer ◽  
...  
Keyword(s):  
Electrostatic Interactions ◽  
Membrane Lipid ◽  
Membrane Curvature ◽  
Caveolin 1 ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Solution Generation ◽  
Endosomal System ◽  
Disordered Regions

AbstractCaveolae are spherically shaped nanodomains of the plasma membrane, generated by cooperative assembly of caveolin and cavin proteins. Cavins are cytosolic peripheral membrane proteins with negatively charged intrinsically disordered regions that flank positively charged α-helical regions. Here, we show that the three disordered domains of Cavin1 are essential for caveola formation and dynamic trafficking of caveolae. Electrostatic interactions between disordered regions and α-helical regions promote liquid-liquid phase separation behaviour of Cavin1 in vitro, assembly of Cavin1 oligomers in solution, generation of membrane curvature, association with caveolin-1, and Cavin1 recruitment to caveolae in cells. Removal of the first disordered region causes irreversible gel formation in vitro and results in aberrant caveola trafficking through the endosomal system. We propose a model for caveola assembly whereby fuzzy electrostatic interactions between Cavin1 and caveolin-1 proteins, combined with membrane lipid interactions, are required to generate membrane curvature and a metastable caveola coat.

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