scholarly journals Theory on the looping mediated directional-dependent propulsion of transcription factors along DNA

2018 ◽  
Author(s):  
R. Murugan
Keyword(s):  
Transcription Factors ◽  
Protein Interactions ◽  
Critical Role ◽  
Protein Protein Interactions ◽  
Bent Dna ◽  
Site Specific ◽  
Combinatorial Regulation ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Nonspecific Interactions

ABSTRACTWe show that the looping mediated transcription activation by the combinatorial transcription factors (TFs) can be achieved via directional-dependent propulsion, tethered sliding and tethered binding-sliding-unbinding modes. In the propulsion mode, the first arrived TF at the cis-regulatory motifs (CRMs) further recruits other TFs via protein-protein interactions. Such TFs complex has two different types of DNA binding domains (DBDs) viz. DBD1 which forms tight site-specific complex with CRMs via hydrogen bonding network and the promoter specific DBD2s which form nonspecific interactions around CRMs. When the sum of these specific and cumulative nonspecific interactions is sufficient, then the flanking DNA of CRMs will be bent into a circle over the TFs complex. The number of TFs involved in the combinatorial regulation plays critical role here. When the site-specific interactions and the cumulative nonspecific interactions are strong enough to resist the dissociation, then the sliding of DBD2s well within the Onsager radius associated with the DBD2s-DNA interface towards the promoter is the only possible way to release the elastic stress of the bent DNA. The DBD2s form tight synaptosome complex upon finding the promoter via sliding. When the number of TFs is not enough to bend the DNA in to a circle, then tethered sliding or tethered binding-sliding-unbinding modes are the possibilities. In tethered sliding, the CRMs-TFs complex forms nonspecific contacts with DNA via dynamic loops and then slide along DNA towards promoter without dissociation. In tethered binding-sliding-unbinding, the CRMs-TFs performs several cycles of nonspecific binding-sliding-unbinding before finding the promoter. Elastic and entropic energy barriers associated with the looping of DNA shape up the distribution of distances between CRMs and promoters. The combinatorial regulation of TFs in eukaryotes has evolved to overcome the looping energy barrier.

scholarly journals Structural Classification of Bacterial Response Regulators: Diversity of Output Domains and Domain Combinations

2006 ◽  
Vol 188 (12) ◽  
pp. 4169-4182 ◽  
Author(s):  
Michael Y. Galperin
Keyword(s):  
Protein Interactions ◽  
Rna Binding ◽  
Transcriptional Regulators ◽  
Bacterial Cells ◽  
Protein Protein Interactions ◽  
Response Regulators ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Archaeal Species

ABSTRACT CheY-like phosphoacceptor (or receiver [REC]) domain is a common module in a variety of response regulators of the bacterial signal transduction systems. In this work, 4,610 response regulators, encoded in complete genomes of 200 bacterial and archaeal species, were identified and classified by their domain architectures. Previously uncharacterized output domains were analyzed and, in some cases, assigned to known domain families. Transcriptional regulators of the OmpR, NarL, and NtrC families were found to comprise almost 60% of all response regulators; transcriptional regulators with other DNA-binding domains (LytTR, AraC, Spo0A, Fis, YcbB, RpoE, and MerR) account for an additional 6%. The remaining one-third is represented by the stand-alone REC domain (∼14%) and its combinations with a variety of enzymatic (GGDEF, EAL, HD-GYP, CheB, CheC, PP2C, and HisK), RNA-binding (ANTAR and CsrA), protein- or ligand-binding (PAS, GAF, TPR, CAP_ED, and HPt) domains, or newly described domains of unknown function. The diversity of domain architectures and the abundance of alternative domain combinations suggest that fusions between the REC domain and various output domains is a widespread evolutionary mechanism that allows bacterial cells to regulate transcription, enzyme activity, and/or protein-protein interactions in response to environmental challenges. The complete list of response regulators encoded in each of the 200 analyzed genomes is available online at http://www.ncbi.nlm.nih.gov/Complete_Genomes/RRcensus.html .

scholarly journals Role of the C-Terminal Binding Protein PXDLS Motif Binding Cleft in Protein Interactions and Transcriptional Repression

2006 ◽  
Vol 26 (21) ◽  
pp. 8202-8213 ◽  
Author(s):  
Kate G. R. Quinlan ◽  
Alexis Verger ◽  
Alister Kwok ◽  
Stella H. Y. Lee ◽  
José Perdomo ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Protein Interactions ◽  
Transcriptional Repression ◽  
Histone Deacetylases ◽  
Gene Repression ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Binding Cleft ◽  
Partner Proteins

ABSTRACT C-terminal binding proteins (CtBPs) are multifunctional proteins that can mediate gene repression. CtBPs contain a cleft that binds Pro-X-Asp-Leu-Ser (PXDLS) motifs. PXDLS motifs occur in numerous transcription factors and in effectors of gene repression, such as certain histone deacetylases. CtBPs have been depicted as bridging proteins that self-associate and link PXDLS-containing transcription factors to PXDLS-containing chromatin-modifying enzymes. CtBPs also recruit effectors that do not contain recognizable PXDLS motifs. We have investigated the importance of the PXDLS binding cleft to CtBP's interactions with various partner proteins and to its ability to repress transcription. We used CtBP cleft mutant and cleft-filled fusion derivatives to distinguish between partner proteins that bind in the cleft and elsewhere on the CtBP surface. Functional assays demonstrate that CtBP mutants that carry defective clefts retain repression activity when fused to heterologous DNA-binding domains. This result suggests that the cleft is not essential for recruiting effectors. In contrast, when tested in the absence of a fused DNA-binding domain, disruption of the cleft abrogates repression activity. These results demonstrate that the PXDLS binding cleft is functionally important but suggest that it is primarily required for localization of the CtBP complex to promoter-bound transcription factors.

scholarly journals Arf•GAPs as Regulators of the Actin Cytoskeleton—An Update

2019 ◽  
Vol 20 (2) ◽  
pp. 442 ◽  
Author(s):  
Christine Tanna ◽  
Louisa Goss ◽  
Calvin Ludwig ◽  
Pei-Wen Chen
Keyword(s):  
Protein Interactions ◽  
Cell Function ◽  
Critical Role ◽  
Focal Adhesions ◽  
Actin Dynamics ◽  
Protein Protein Interactions ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
Binding Domains ◽  
Multiple Protein

Arf•GTPase-activating proteins (Arf•GAPs) control the activity of ADP-ribosylation factors (Arfs) by inducing GTP hydrolysis and participate in a diverse array of cellular functions both through mechanisms that are dependent on and independent of their Arf•GAP activity. A number of these functions hinge on the remodeling of actin filaments. Accordingly, some of the effects exerted by Arf•GAPs involve proteins known to engage in regulation of the actin dynamics and architecture, such as Rho family proteins and nonmuscle myosin 2. Circular dorsal ruffles (CDRs), podosomes, invadopodia, lamellipodia, stress fibers and focal adhesions are among the actin-based structures regulated by Arf•GAPs. Arf•GAPs are thus important actors in broad functions like adhesion and motility, as well as the specialized functions of bone resorption, neurite outgrowth, and pathogen internalization by immune cells. Arf•GAPs, with their multiple protein-protein interactions, membrane-binding domains and sites for post-translational modification, are good candidates for linking the changes in actin to the membrane. The findings discussed depict a family of proteins with a critical role in regulating actin dynamics to enable proper cell function.

Protein-protein interactions between the DNA-binding domains of nuclear receptors: Influence on DNA-binding

1993 ◽  
Vol 45 (4) ◽  
pp. 239-250 ◽  
Author(s):  
Karin Dahlman-Wright ◽  
Kaj Grandien ◽  
Stefan Nilsson ◽  
Jan-Åke Gustafsson ◽  
Jan Carlstedt-Duke
Keyword(s):  
Dna Binding ◽  
Nuclear Receptors ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Dna Binding Domains ◽  
Binding Domains

scholarly journals The Roles of Arabidopsis C1-2i Subclass of C2H2-type Zinc-Finger Transcription Factors

Genes ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 653 ◽  
Author(s):  
Minmin Xie ◽  
Jinhao Sun ◽  
Daping Gong ◽  
Yingzhen Kong
Keyword(s):  
Transcription Factors ◽  
Zinc Finger ◽  
Protein Interactions ◽  
Stress Responses ◽  
Zinc Finger Protein ◽  
Critical Role ◽  
Protein Protein Interactions ◽  
Gcc Box ◽  
Tolerance Response ◽  
Defense Research

The Cys2His2 (C2H2)-type zinc-finger protein (ZFP) family, which includes 176 members in Arabidopsis thaliana, is one of the largest families of putative transcription factors in plants. Of the Arabidopsis ZFP members, only 33 members are conserved in other eukaryotes, with 143 considered to be plant specific. C2H2-type ZFPs have been extensively studied and have been shown to play important roles in plant development and environmental stress responses by transcriptional regulation. The ethylene-responsive element binding-factor-associated amphiphilic repression (EAR) domain (GCC box) has been found to have a critical role in the tolerance response to abiotic stress. Many of the plant ZFPs containing the EAR domain, such as AZF1/2/3, ZAT7, ZAT10, and ZAT12, have been shown to function as transcriptional repressors. In this review, we mainly focus on the C1-2i subclass of C2H2 ZFPs and summarize the latest research into their roles in various stress responses. The role of C2H2-type ZFPs in response to the abiotic and biotic stress signaling network is not well explained, and amongst them, C1-2i is one of the better-characterized classifications in response to environmental stresses. These studies of the C1-2i subclass ought to furnish the basis for future studies to discover the pathways and receptors concerned in stress defense. Research has implied possible protein-protein interactions between members of C1-2i under various stresses, for which we have proposed a hypothetical model.

Exploring Proteomic Drug Targets, Therapeutic Strategies and Protein - Protein Interactions in Cancer: Mechanistic View

2019 ◽  
Vol 19 (6) ◽  
pp. 430-448 ◽  
Author(s):  
Khalid Bashir Dar ◽  
Aashiq Hussain Bhat ◽  
Shajrul Amin ◽  
Syed Anjum ◽  
Bilal Ahmad Reshi ◽  
...  
Keyword(s):  
Protein Interactions ◽  
High Throughput Screening ◽  
Critical Role ◽  
Cancer Therapeutics ◽  
Adaptor Proteins ◽  
Therapeutic Strategies ◽  
Small Gtpases ◽  
Beta Catenin ◽  
Protein Protein Interactions ◽  
Apoptosis Protein

Protein-Protein Interactions (PPIs) drive major signalling cascades and play critical role in cell proliferation, apoptosis, angiogenesis and trafficking. Deregulated PPIs are implicated in multiple malignancies and represent the critical targets for treating cancer. Herein, we discuss the key protein-protein interacting domains implicated in cancer notably PDZ, SH2, SH3, LIM, PTB, SAM and PH. These domains are present in numerous enzymes/kinases, growth factors, transcription factors, adaptor proteins, receptors and scaffolding proteins and thus represent essential sites for targeting cancer. This review explores the candidature of various proteins involved in cellular trafficking (small GTPases, molecular motors, matrix-degrading enzymes, integrin), transcription (p53, cMyc), signalling (membrane receptor proteins), angiogenesis (VEGFs) and apoptosis (BCL-2family), which could possibly serve as targets for developing effective anti-cancer regimen. Interactions between Ras/Raf; X-linked inhibitor of apoptosis protein (XIAP)/second mitochondria-derived activator of caspases (Smac/DIABLO); Frizzled (FRZ)/Dishevelled (DVL) protein; beta-catenin/T Cell Factor (TCF) have also been studied as prospective anticancer targets. Efficacy of diverse molecules/ drugs targeting such PPIs although evaluated in various animal models/cell lines, there is an essential need for human-based clinical trials. Therapeutic strategies like the use of biologicals, high throughput screening (HTS) and fragment-based technology could play an imperative role in designing cancer therapeutics. Moreover, bioinformatic/computational strategies based on genome sequence, protein sequence/structure and domain data could serve as competent tools for predicting PPIs. Exploring hot spots in proteomic networks represents another approach for developing targetspecific therapeutics. Overall, this review lays emphasis on a productive amalgamation of proteomics, genomics, biochemistry, and molecular dynamics for successful treatment of cancer.

scholarly journals Mechanistic Heterogeneity in Site Recognition by the Structurally Homologous DNA-binding Domains of the ETS Family Transcription Factors Ets-1 and PU.1

2014 ◽  
Vol 289 (31) ◽  
pp. 21605-21616 ◽  
Author(s):  
Shuo Wang ◽  
Miles H. Linde ◽  
Manoj Munde ◽  
Victor D. Carvalho ◽  
W. David Wilson ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Ets Family ◽  
Site Recognition
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