Comparative analysis of human and mouse transcriptional cofactors (TcoFs) with special emphasis on intrinsically disordered regions and their associated regulating post-translational modifications

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.

3SEA-05 The interaction between transcription factors Sp1 and TAF4 via the intrinsically disordered regions(Frontiers in physical properties of proteins: challenges by young scientists,Symposium,The 52th Annual Meeting of the Biophysical Society of Japan(BSJ2014))

Seibutsu Butsuri ◽

10.2142/biophys.54.s140_4 ◽

2014 ◽

Vol 54 (supplement1-2) ◽

pp. S140

Author(s):

Emi Hibino ◽

Rintaro Inoue ◽

Masaaki Sugiyama ◽

Jun Kuwahara ◽

Katsumi Matsuzaki ◽

...

Keyword(s):

Transcription Factors ◽

Physical Properties ◽

Annual Meeting ◽

Intrinsically Disordered ◽

Intrinsically Disordered Regions ◽

Biophysical Society ◽

Disordered Regions

Basic Residue Clusters in Intrinsically Disordered Regions of Peripheral Membrane Proteins: Modulating 2D Diffusion on Cell Membranes

Physchem ◽

10.3390/physchem1020010 ◽

2021 ◽

Vol 1 (2) ◽

pp. 152-162

Author(s):

Miquel Pons

Keyword(s):

Membrane Proteins ◽

Electrostatic Interactions ◽

Lipid Membrane ◽

Conformational Ensemble ◽

Basic Residue ◽

Intrinsically Disordered ◽

Intrinsically Disordered Regions ◽

Peripheral Membrane Proteins ◽

Charged Residues ◽

Disordered Regions

A large number of peripheral membrane proteins transiently interact with lipids through a combination of weak interactions. Among them, electrostatic interactions of clusters of positively charged amino acid residues with negatively charged lipids play an important role. Clusters of charged residues are often found in intrinsically disordered protein regions, which are highly abundant in the vicinity of the membrane forming what has been called the disordered boundary of the cell. Beyond contributing to the stability of the lipid-bound state, the pattern of charged residues may encode specific interactions or properties that form the basis of cell signaling. The element of this code may include, among others, the recognition, clustering, and selective release of phosphatidyl inositides, lipid-mediated protein-protein interactions changing the residence time of the peripheral membrane proteins or driving their approximation to integral membrane proteins. Boundary effects include reduction of dimensionality, protein reorientation, biassing of the conformational ensemble of disordered regions or enhanced 2D diffusion in the peri-membrane region enabled by the fuzzy character of the electrostatic interactions with an extended lipid membrane.

Visualising intrinsic disorder and conformational variation in protein ensembles

Faraday Discussions ◽

10.1039/c3fd00138e ◽

2014 ◽

Vol 169 ◽

pp. 179-193 ◽

Cited By ~ 6

Author(s):

Julian Heinrich ◽

Michael Krone ◽

Seán I. O'Donoghue ◽

Daniel Weiskopf

Keyword(s):

Intrinsic Disorder ◽

Molecular Graphics ◽

Post Translational Modifications ◽

3D Structures ◽

Intrinsically Disordered ◽

Intrinsically Disordered Regions ◽

Wide Range ◽

Conformational Variations ◽

Protein Ensembles ◽

Traditional Approaches

Intrinsically disordered regions (IDRs) in proteins are still not well understood, but are increasingly recognised as important in key biological functions, as well as in diseases. IDRs often confound experimental structure determination—however, they are present in many of the available 3D structures, where they exhibit a wide range of conformations, from ill-defined and highly flexible to well-defined upon binding to partner molecules, or upon post-translational modifications. Analysing such large conformational variations across ensembles of 3D structures can be complex and difficult; our goal in this paper is to improve this situation by augmenting traditional approaches (molecular graphics and principal components) with methods from human–computer interaction and information visualisation, especially parallel coordinates. We present a new tool integrating these approaches, and demonstrate how it can dissect ensembles to reveal functional insights into conformational variation and intrinsic disorder.