scholarly journals Analysis of structured and intrinsically disordered regions of transmembrane proteins

2009 ◽  
Vol 5 (12) ◽  
pp. 1688 ◽  
Author(s):  
Bin Xue ◽  
Liwei Li ◽  
Samy O. Meroueh ◽  
Vladimir N. Uversky ◽  
A. Keith Dunker
Keyword(s):  
Transmembrane Proteins ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Disordered Regions

scholarly journals MemDis: Predicting Disordered Regions in Transmembrane Proteins

2021 ◽  
Vol 22 (22) ◽  
pp. 12270
Author(s):  
Laszlo Dobson ◽  
Gábor E. Tusnády
Keyword(s):  
Short Term Memory ◽  
Transmembrane Proteins ◽  
Chemical Properties ◽  
Prediction Method ◽  
Transport Processes ◽  
Prediction Methods ◽  
X Ray Crystallography ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Disordered Regions

Transmembrane proteins (TMPs) play important roles in cells, ranging from transport processes and cell adhesion to communication. Many of these functions are mediated by intrinsically disordered regions (IDRs), flexible protein segments without a well-defined structure. Although a variety of prediction methods are available for predicting IDRs, their accuracy is very limited on TMPs due to their special physico-chemical properties. We prepared a dataset containing membrane proteins exclusively, using X-ray crystallography data. MemDis is a novel prediction method, utilizing convolutional neural network and long short-term memory networks for predicting disordered regions in TMPs. In addition to attributes commonly used in IDR predictors, we defined several TMP specific features to enhance the accuracy of our method further. MemDis achieved the highest prediction accuracy on TMP-specific dataset among other popular IDR prediction methods.

scholarly journals Mutations in disordered regions cause disease by creating endocytosis motifs

2017 ◽  
Author(s):  
Katrina Meyer ◽  
Bora Uyar ◽  
Marieluise Kirchner ◽  
Jingyuan Cheng ◽  
Altuna Akalin ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Wide Spectrum ◽  
Transmembrane Proteins ◽  
Dimensional Structure ◽  
Systematic Analysis ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Dileucine Motif ◽  
The Impact ◽  
Disordered Regions

AbstractMutations in intrinsically disordered regions (IDRs) of proteins can cause a wide spectrum of diseases. Since IDRs lack a fixed three-dimensional structure, the mechanism by which such mutations cause disease is often unknown. Here, we employ a proteomic screen to investigate the impact of mutations in IDRs on protein-protein interactions. We find that mutations in disordered cytosolic regions of three transmembrane proteins (GLUT1, ITPR1 and CACNA1H) lead to an increased binding of clathrins. In all three cases, the mutation creates a dileucine motif known to mediate clathrin-dependent trafficking. Follow-up experiments on GLUT1 (SLC2A1), a glucose transporter involved in GLUT1 deficiency syndrome, revealed that the mutated protein mislocalizes to intracellular compartments. A systematic analysis of other known disease-causing variants revealed a significant and specific overrepresentation of gained dileucine motifs in cytosolic tails of transmembrane proteins. Dileucine motif gains thus appear to be a recurrent cause of disease.

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.

Sign in / Sign up

Export Citation Format

Share Document