scholarly journals Transcriptional Repressor Domain of MBD1 is Intrinsically Disordered and Interacts with its Binding Partners in a Selective Manner

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Umar Farook Shahul Hameed ◽  
Jackwee Lim ◽  
Qian Zhang ◽  
Mariusz A. Wasik ◽  
Daiwen Yang ◽  
...  
Keyword(s):  
Transcriptional Repressor ◽  
Intrinsically Disordered ◽  
Binding Partners ◽  
Transcriptional Repressor Domain

scholarly journals The Transcriptional Repressor Domain of Gli3 Is Intrinsically Disordered

PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e76972 ◽  
Author(s):  
Robert Tsanev ◽  
Kalju Vanatalu ◽  
Jüri Jarvet ◽  
Risto Tanner ◽  
Kristi Laur ◽  
...  
Keyword(s):  
Transcriptional Repressor ◽  
Intrinsically Disordered ◽  
Transcriptional Repressor Domain

scholarly journals Functional Heme Binding to the Intrinsically Disordered C-Terminal Region of Bach1, a Transcriptional Repressor

2019 ◽  
Vol 247 (3) ◽  
pp. 153-159
Author(s):  
Kei Segawa ◽  
Miki Watanabe-Matsui ◽  
Toshitaka Matsui ◽  
Kazuhiko Igarashi ◽  
Kazutaka Murayama
Keyword(s):  
Transcriptional Repressor ◽  
Terminal Region ◽  
Heme Binding ◽  
Intrinsically Disordered

scholarly journals The Disordered Cellular Multi-Tasker WIP and Its Protein–Protein Interactions: A Structural View

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1084 ◽  
Author(s):  
Chana G. Sokolik ◽  
Nasrin Qassem ◽  
Jordan H. Chill
Keyword(s):  
Protein Interactions ◽  
Cell Biology ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Actin Binding ◽  
Structural Description ◽  
Protein Protein Interactions ◽  
Intrinsically Disordered ◽  
Terminal Domain ◽  
Binding Partners

WASp-interacting protein (WIP), a regulator of actin cytoskeleton assembly and remodeling, is a cellular multi-tasker and a key member of a network of protein–protein interactions, with significant impact on health and disease. Here, we attempt to complement the well-established understanding of WIP function from cell biology studies, summarized in several reviews, with a structural description of WIP interactions, highlighting works that present a molecular view of WIP’s protein–protein interactions. This provides a deeper understanding of the mechanisms by which WIP mediates its biological functions. The fully disordered WIP also serves as an intriguing example of how intrinsically disordered proteins (IDPs) exert their function. WIP consists of consecutive small functional domains and motifs that interact with a host of cellular partners, with a striking preponderance of proline-rich motif capable of interactions with several well-recognized binding partners; indeed, over 30% of the WIP primary structure are proline residues. We focus on the binding motifs and binding interfaces of three important WIP segments, the actin-binding N-terminal domain, the central domain that binds SH3 domains of various interaction partners, and the WASp-binding C-terminal domain. Beyond the obvious importance of a more fundamental understanding of the biology of this central cellular player, this approach carries an immediate and highly beneficial effect on drug-design efforts targeting WIP and its binding partners. These factors make the value of such structural studies, challenging as they are, readily apparent.

Transiently transfected and stably integrated HIV-1 LTR responds differentially to the silencing activity of the Kr�ppel-associated box (KRAB) transcriptional repressor domain

1999 ◽  
Vol 58 (3) ◽  
pp. 264-272 ◽  
Author(s):  
Cristina Rossi ◽  
Davide Gibellini ◽  
Giuseppe Barbanti-Brodano ◽  
Monica Betti ◽  
Chiara Boarini ◽  
...  
Keyword(s):  
Transcriptional Repressor ◽  
Transcriptional Repressor Domain ◽  
Hiv 1

scholarly journals Dynamics in Fip1 regulate eukaryotic mRNA 3'-end processing

2021 ◽  
Author(s):  
Ananthanarayanan Kumar ◽  
Conny WH Yu ◽  
Juan B Rodríguez-Molina ◽  
Xiao-Han Li ◽  
Stefan MV Freund ◽  
...  
Keyword(s):  
Binding Sites ◽  
Conformational Transitions ◽  
Resonance Spectroscopy ◽  
Multiprotein Complex ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Binding Partners ◽  
Single Protein ◽  
Cleavage And Polyadenylation ◽  
Polyadenylation Factor

Cleavage and polyadenylation factor (CPF/CPSF) is a multiprotein complex essential for mRNA 3ʹ-end processing in eukaryotes. It contains an endonuclease that cleaves pre-mRNAs, and a polymerase that adds a poly(A) tail onto the cleaved 3ʹ-end. Several CPF subunits, including Fip1, contain intrinsically-disordered regions (IDRs). IDRs within multiprotein complexes can be flexible, or can become ordered upon interaction with binding partners. Here, we show that yeast Fip1 anchors the poly(A) polymerase Pap1 onto CPF via an interaction with zinc finger 4 of another CPF subunit, Yth1. We also reconstitute a fully recombinant 850-kDa CPF. By incorporating selectively-labelled Fip1 into recombinant CPF, we could study the dynamics of this single protein within the megadalton complex using nuclear magnetic resonance spectroscopy (NMR). This reveals that a Fip1 IDR that connects the Yth1- and Pap1-binding sites remains highly dynamic within CPF. Together, our data suggest that Fip1 dynamics mediate conformational transitions within the 3ʹ-end processing machinery to coordinate cleavage and polyadenylation.

scholarly journals Evolution of an interaction between disordered proteins resulted in increased heterogeneity of the binding transition state

2020 ◽  
Author(s):  
Elin Karlsson ◽  
Cristina Paissoni ◽  
Amanda M. Erkelens ◽  
Zeinab Amiri Tehranizadeh ◽  
Frieda A. Sorgenfrei ◽  
...  
Keyword(s):  
Transition State ◽  
Intrinsically Disordered Protein ◽  
Disordered Proteins ◽  
Hydrophobic Contact ◽  
Intrinsically Disordered ◽  
High Affinity ◽  
Binding Partners ◽  
Multiple Binding ◽  
Multiple Alternative ◽  
Transient Interactions

AbstractIntrinsically disordered protein (IDP) domains often have multiple binding partners. Little is known regarding molecular changes in the binding mechanism when a new interaction evolves from low to high affinity. Here we compared the degree of native contacts in the transition state of the interaction of two IDP domains, low-affinity ancestral and high-affinity human NCBD and CID. We found that the coupled binding and folding mechanism of the domains is overall similar, but with a higher degree of native hydrophobic contact formation in the transition state of the ancestral complex while more heterogenous transient interactions, including electrostatic, and an increased disorder characterize the human complex. From an evolutionary perspective, adaptation to new binding partners for IDPs may benefit from this ability to exploit multiple alternative transient interactions while retaining the overall pathway.

scholarly journals Caulobacter PopZ forms an intrinsically disordered hub in organizing bacterial cell poles

2016 ◽  
Vol 113 (44) ◽  
pp. 12490-12495 ◽  
Author(s):  
Joshua A. Holmes ◽  
Shelby E. Follett ◽  
Haibi Wang ◽  
Christopher P. Meadows ◽  
Krisztina Varga ◽  
...  
Keyword(s):  
Caulobacter Crescentus ◽  
Intrinsically Disordered ◽  
Binding Partners ◽  
Complex Anatomy ◽  
Oligomeric Assembly ◽  
Complex Signaling ◽  
Cycle Regulation ◽  
Binding Determinants ◽  
Hub Proteins ◽  
Rapid Binding

Despite their relative simplicity, bacteria have complex anatomy at the subcellular level. At the cell poles of Caulobacter crescentus, a 177-amino acid (aa) protein called PopZ self-assembles into 3D polymeric superstructures. Remarkably, we find that this assemblage interacts directly with at least eight different proteins, which are involved in cell cycle regulation and chromosome segregation. The binding determinants within PopZ include 24 aa at the N terminus, a 32-aa region near the C-terminal homo-oligomeric assembly domain, and portions of an intervening linker region. Together, the N-terminal 133 aa of PopZ are sufficient for interacting with all binding partners, even in the absence of homo-oligomeric assembly. Structural analysis of this region revealed that it is intrinsically disordered, similar to p53 and other hub proteins that organize complex signaling networks in eukaryotic cells. Through live-cell photobleaching, we find rapid binding kinetics between PopZ and its partners, suggesting many pole-localized proteins become concentrated at cell poles through rapid cycles of binding and unbinding within the PopZ scaffold. We conclude that some bacteria, similar to their eukaryotic counterparts, use intrinsically disordered hub proteins for network assembly and subcellular organization.

scholarly journals Mapping the transition state for a binding reaction between ancient intrinsically disordered proteins

2020 ◽  
Vol 295 (51) ◽  
pp. 17698-17712
Author(s):  
Elin Karlsson ◽  
Cristina Paissoni ◽  
Amanda M. Erkelens ◽  
Zeinab A. Tehranizadeh ◽  
Frieda A. Sorgenfrei ◽  
...  
Keyword(s):  
Transition State ◽  
Intrinsically Disordered Proteins ◽  
Intrinsically Disordered Protein ◽  
Disordered Proteins ◽  
Hydrophobic Contact ◽  
Intrinsically Disordered ◽  
Binding Partners ◽  
Multiple Alternative ◽  
Transient Interactions ◽  
Affinity Interaction

Intrinsically disordered protein domains often have multiple binding partners. It is plausible that the strength of pairing with specific partners evolves from an initial low affinity to a higher affinity. However, little is known about the molecular changes in the binding mechanism that would facilitate such a transition. We previously showed that the interaction between two intrinsically disordered domains, NCBD and CID, likely emerged in an ancestral deuterostome organism as a low-affinity interaction that subsequently evolved into a higher-affinity interaction before the radiation of modern vertebrate groups. Here we map native contacts in the transition states of the low-affinity ancestral and high-affinity human NCBD/CID interactions. We show that the coupled binding and folding mechanism is overall similar but with a higher degree of native hydrophobic contact formation in the transition state of the ancestral complex and more heterogeneous transient interactions, including electrostatic pairings, and an increased disorder for the human complex. Adaptation to new binding partners may be facilitated by this ability to exploit multiple alternative transient interactions while retaining the overall binding and folding pathway.

scholarly journals On the specificity of protein–protein interactions in the context of disorder

2021 ◽  
Vol 478 (11) ◽  
pp. 2035-2050
Author(s):  
Kaare Teilum ◽  
Johan G. Olsen ◽  
Birthe B. Kragelund
Keyword(s):  
Protein Interactions ◽  
Intrinsically Disordered Proteins ◽  
Globular Proteins ◽  
Disordered Proteins ◽  
Protein Protein Interactions ◽  
Binding Motifs ◽  
Intrinsically Disordered ◽  
Binding Partners ◽  
Trimer Formation ◽  
Definition Of

With the increased focus on intrinsically disordered proteins (IDPs) and their large interactomes, the question about their specificity — or more so on their multispecificity — arise. Here we recapitulate how specificity and multispecificity are quantified and address through examples if IDPs in this respect differ from globular proteins. The conclusion is that quantitatively, globular proteins and IDPs are similar when it comes to specificity. However, compared with globular proteins, IDPs have larger interactome sizes, a phenomenon that is further enabled by their flexibility, repetitive binding motifs and propensity to adapt to different binding partners. For IDPs, this adaptability, interactome size and a higher degree of multivalency opens for new interaction mechanisms such as facilitated exchange through trimer formation and ultra-sensitivity via threshold effects and ensemble redistribution. IDPs and their interactions, thus, do not compromise the definition of specificity. Instead, it is the sheer size of their interactomes that complicates its calculation. More importantly, it is this size that challenges how we conceptually envision, interpret and speak about their specificity.

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