Dynamics, Conformational Entropy, and Frustration in Protein–Protein Interactions Involving an Intrinsically Disordered Protein Domain

2018 ◽  
Vol 13 (5) ◽  
pp. 1218-1227 ◽  
Author(s):  
Ida Lindström ◽  
Jakob Dogan
Keyword(s):  
Protein Interactions ◽  
Intrinsically Disordered Protein ◽  
Protein Domain ◽  
Protein Protein Interactions ◽  
Conformational Entropy ◽  
Intrinsically Disordered ◽  
Disordered Protein

scholarly journals Coordination of RNA and protein condensation by the P granule protein MEG-3

2020 ◽  
Author(s):  
Helen Schmidt ◽  
Andrea Putnam ◽  
Dominique Rasoloson ◽  
Geraldine Seydoux
Keyword(s):  
Protein Interactions ◽  
Intrinsically Disordered Protein ◽  
Protein Protein Interactions ◽  
C Elegans ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
C Terminus ◽  
Necessary And Sufficient

ABSTRACTGerm granules are RNA-protein condensates in germ cells. The mechanisms that drive germ granule assembly are not fully understood. MEG-3 is an intrinsically-disordered protein required for germ (P) granule assembly in C. elegans. MEG-3 forms gel-like condensates on liquid condensates assembled by PGL proteins. MEG-3 is related to the GCNA family and contains an N-terminal disordered region (IDR) and a predicted ordered C-terminus featuring an HMG-like motif (HMGL). Using in vitro and in vivo experiments, we find the MEG-3 C-terminus is necessary and sufficient to build MEG-3/PGL co-condensates independent of RNA. The HMGL domain is required for high affinity MEG-3/PGL binding in vitro and for assembly of MEG-3/PGL co-condensates in vivo. The MEG-3 IDR binds RNA in vitro and is required but not sufficient to recruit RNA to P granules. Our findings suggest that P granule assembly depends in part on protein-protein interactions that drive condensation independent of RNA.

scholarly journals Fuzzy regions in an intrinsically disordered protein impair protein-protein interactions

FEBS Journal ◽  
2016 ◽  
Vol 283 (4) ◽  
pp. 576-594 ◽  
Author(s):  
Antoine Gruet ◽  
Marion Dosnon ◽  
David Blocquel ◽  
Joanna Brunel ◽  
Denis Gerlier ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Intrinsically Disordered Protein ◽  
Protein Protein Interactions ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Fuzzy Regions

scholarly journals Functional dissection of an intrinsically disordered protein: Understanding the roles of different domains of Knr4 protein in protein-protein interactions

2010 ◽  
Vol 19 (7) ◽  
pp. 1376-1385 ◽  
Author(s):  
Adilia Dagkessamanskaia ◽  
Fabien Durand ◽  
Vladimir N. Uversky ◽  
Matteo Binda ◽  
Frédéric Lopez ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Intrinsically Disordered Protein ◽  
Protein Protein Interactions ◽  
Intrinsically Disordered ◽  
Disordered Protein

scholarly journals α-carboxysome formation is mediated by the multivalent and disordered protein CsoS2

2019 ◽  
Author(s):  
Luke M. Oltrogge ◽  
Thawatchai Chaijarasphong ◽  
Allen W. Chen ◽  
Eric R. Bolin ◽  
Susan Marqusee ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Electrostatic Interactions ◽  
Intrinsically Disordered Protein ◽  
Peptide Sequence ◽  
Protein Protein Interactions ◽  
X Ray ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
High Concentrations ◽  
Insight Into

AbstractCarboxysomes are bacterial microcompartments that function as the centerpiece of the bacterial CO2-concentrating mechanism, feeding high concentrations of CO2 to the enzyme Rubisco for fixation. The carboxysome self-assembles from thousands of individual proteins into icosahedral-like particles with a dense enzyme cargo encapsulated within a proteinaceous shell. In the case of the α-carboxysome, there is little molecular insight into protein-protein interactions which drive the assembly process. Here we show that the N-terminus of CsoS2, an intrinsically disordered protein found in the α-carboxysome, possesses a repeated peptide sequence that binds Rubisco. X-ray structural analysis of the peptide bound to Rubisco reveals a series of conserved electrostatic interactions that are only made with properly assembled hexadecameric Rubisco. Although biophysical measurements indicate this single interaction is weak, its implicit multivalency induces high-affinity binding through avidity. Taken together, our results indicate CsoS2 acts as an interaction hub to condense Rubisco and enable efficient α-carboxysome formation.

Self-Assembling Micelles Based on an Intrinsically Disordered Protein Domain

2018 ◽  
Author(s):  
Sarah Klass ◽  
Matthew J. Smith ◽  
Tahoe Fiala ◽  
Jessica Lee ◽  
Anthony Omole ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Fusion Proteins ◽  
Organic Molecules ◽  
Intrinsically Disordered Protein ◽  
Protein Domain ◽  
Enzymatic Cleavage ◽  
Intrinsically Disordered ◽  
Disordered Protein ◽  
Self Assembling ◽  
Protein Tag

Herein, we describe a new series of fusion proteins that have been developed to self-assemble spontaneously into stable micelles that are 27 nm in diameter after enzymatic cleavage of a solubilizing protein tag. The sequences of the proteins are based on a human intrinsically disordered protein, which has been appended with a hydrophobic segment. The micelles were found to form across a broad range of pH, ionic strength, and temperature conditions, with critical micelle concentration (CMC) values below 1 µM being observed in some cases. The reported micelles were found to solubilize hydrophobic metal complexes and organic molecules, suggesting their potential suitability for catalysis and drug delivery applications.

scholarly journals Intrinsic Disorder in Tetratricopeptide Repeat Proteins

2020 ◽  
Vol 21 (10) ◽  
pp. 3709 ◽  
Author(s):  
Nathan W. Van Bibber ◽  
Cornelia Haerle ◽  
Roy Khalife ◽  
Bin Xue ◽  
Vladimir N. Uversky
Keyword(s):  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Tandem Repeats ◽  
Intrinsically Disordered Protein ◽  
Intrinsic Disorder ◽  
Protein Protein Interactions ◽  
Systematic Analysis ◽  
Tetratricopeptide Repeats ◽  
Intrinsically Disordered ◽  
Tetratricopeptide Repeat Proteins

Among the realm of repeat containing proteins that commonly serve as “scaffolds” promoting protein-protein interactions, there is a family of proteins containing between 2 and 20 tetratricopeptide repeats (TPRs), which are functional motifs consisting of 34 amino acids. The most distinguishing feature of TPR domains is their ability to stack continuously one upon the other, with these stacked repeats being able to affect interaction with binding partners either sequentially or in combination. It is known that many repeat-containing proteins are characterized by high levels of intrinsic disorder, and that many protein tandem repeats can be intrinsically disordered. Furthermore, it seems that TPR-containing proteins share many characteristics with hybrid proteins containing ordered domains and intrinsically disordered protein regions. However, there has not been a systematic analysis of the intrinsic disorder status of TPR proteins. To fill this gap, we analyzed 166 human TPR proteins to determine the degree to which proteins containing TPR motifs are affected by intrinsic disorder. Our analysis revealed that these proteins are characterized by different levels of intrinsic disorder and contain functional disordered regions that are utilized for protein-protein interactions and often serve as targets of various posttranslational modifications.

Affinity versus specificity in coupled binding and folding reactions

2019 ◽  
Author(s):  
Stefano Gianni ◽  
Per Jemth
Keyword(s):  
Protein Interactions ◽  
Intrinsically Disordered Proteins ◽  
Intrinsically Disordered Protein ◽  
High Specificity ◽  
Disordered Proteins ◽  
Protein Protein Interactions ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Interaction Interface ◽  
Disordered Regions

Abstract Intrinsically disordered protein regions may fold upon binding to an interaction partner. It is often argued that such coupled binding and folding enables the combination of high specificity with low affinity. The basic tenet is that an unfavorable folding equilibrium will make the overall binding weaker while maintaining the interaction interface. While theoretically solid, we argue that this concept may be misleading for intrinsically disordered proteins. In fact, experimental evidence suggests that interactions of disordered regions usually involve extended conformations. In such cases, the disordered region is exceptionally unlikely to fold into a bound conformation in the absence of its binding partner. Instead, these disordered regions can bind to their partners in multiple different conformations and then fold into the native bound complex, thus, if anything, increasing the affinity through folding. We concede that (de)stabilization of native structural elements such as helices will modulate affinity, but this could work both ways, decreasing or increasing the stability of the complex. Moreover, experimental data show that intrinsically disordered binding regions display a range of affinities and specificities dictated by the particular side chains and length of the disordered region and not necessarily by the fact that they are disordered. We find it more likely that intrinsically disordered regions are common in protein–protein interactions because they increase the repertoire of binding partners, providing an accessible route to evolve interactions rather than providing a stability–affinity trade-off.

scholarly journals The disordered boundary of the cell: emerging properties of membrane-bound intrinsically disordered proteins

2019 ◽  
Vol 10 (1) ◽  
pp. 25-36 ◽  
Author(s):  
Irrem-Laareb Mohammad ◽  
Borja Mateos ◽  
Miquel Pons
Keyword(s):  
Lipid Bilayers ◽  
Protein Interactions ◽  
Intrinsically Disordered Proteins ◽  
Intrinsically Disordered Protein ◽  
Disordered Proteins ◽  
Protein Protein Interactions ◽  
Intrinsically Disordered ◽  
High Concentrations ◽  
The Individual ◽  
Confined Environment

AbstractWe define the disordered boundary of the cell (DBC) as the system formed by membrane tethered intrinsically disordered protein regions, dynamically coupled to the underlying membrane.The emerging properties of the DBC makes it a global system of study, which cannot be understood from the individual properties of their components. Similarly, the properties of lipid bilayers cannot be understood from just the sum of the properties of individual lipid molecules.The highly anisotropic confined environment, restricting the position and orientation of interacting sites, is affecting the properties of individual disordered proteins. In fact, the collective effect caused by high concentrations of disordered proteins extend beyond the sum of individual effects.Examples of emerging properties of the DBC include enhanced protein-protein interactions, protein-driven phase separations, Z-compartmentalization, and protein modulated electrostatics.

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