Intrinsically Disordered Regions of Human Plasma Membrane Proteins Preferentially Occur in the Cytoplasmic Segment

2007 ◽  
Vol 368 (3) ◽  
pp. 902-913 ◽  
Author(s):  
Yoshiaki Minezaki ◽  
Keiichi Homma ◽  
Ken Nishikawa
Keyword(s):  
Plasma Membrane ◽  
Membrane Proteins ◽  
Human Plasma ◽  
Plasma Membrane Proteins ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Disordered Regions

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

Physchem ◽  
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.

scholarly journals Computational modeling suggests binding-induced expansion of Epsin disordered regions upon association with AP2

2021 ◽  
Vol 17 (1) ◽  
pp. e1008474
Author(s):  
N. Suhas Jagannathan ◽  
Christopher W. V. Hogue ◽  
Lisa Tucker-Kellogg
Keyword(s):  
Plasma Membrane ◽  
Computational Modeling ◽  
Adaptor Protein ◽  
Radius Of Gyration ◽  
Vesicle Formation ◽  
Binding Motifs ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
End Distance ◽  
Disordered Regions

Intrinsically disordered regions (IDRs) are prevalent in the eukaryotic proteome. Common functional roles of IDRs include forming flexible linkers or undergoing allosteric folding-upon-binding. Recent studies have suggested an additional functional role for IDRs: generating steric pressure on the plasma membrane during endocytosis, via molecular crowding. However, in order to accomplish useful functions, such crowding needs to be regulated in space (e.g., endocytic hotspots) and time (e.g., during vesicle formation). In this work, we explore binding-induced regulation of IDR steric volume. We simulate the IDRs of two proteins from Clathrin-mediated endocytosis (CME) to see if their conformational spaces are regulated via binding-induced expansion. Using Monte-Carlo computational modeling of excluded volumes, we generate large conformational ensembles (3 million) for the IDRs of Epsin and Eps15 and dock the conformers to the alpha subunit of Adaptor Protein 2 (AP2α), their CME binding partner. Our results show that as more molecules of AP2α are bound, the Epsin-derived ensemble shows a significant increase in global dimensions, measured as the radius of Gyration (RG) and the end-to-end distance (EED). Unlike Epsin, Eps15-derived conformers that permit AP2α binding at one motif were found to be more likely to accommodate binding of AP2α at other motifs, suggesting a tendency toward co-accessibility of binding motifs. Co-accessibility was not observed for any pair of binding motifs in Epsin. Thus, we speculate that the disordered regions of Epsin and Eps15 perform different roles during CME, with accessibility in Eps15 allowing it to act as a recruiter of AP2α molecules, while binding-induced expansion of the Epsin disordered region could impose steric pressure and remodel the plasma membrane during vesicle formation.

Sign in / Sign up

Export Citation Format

Share Document