The transcription regulator BrsR serves as a network hub of natural competence protein–protein interactions in Streptococcus mutans

2021 ◽  
Vol 118 (39) ◽  
pp. e2106048118
Author(s):  
Hua Qin ◽  
Zhengzhong Zou ◽  
David Anderson ◽  
Yu Sang ◽  
Dustin Higashi ◽  
...  
Keyword(s):  
Genome Evolution ◽  
Streptococcus Mutans ◽  
Protein Interactions ◽  
Adaptor Protein ◽  
Dna Uptake ◽  
Protein Protein Interactions ◽  
Transcription Activator ◽  
Natural Competence ◽  
Transcription Regulator ◽  
Regulatory Circuit

Genome evolution is an essential and stringently regulated aspect of biological fitness. For bacteria, natural competence is one of the principal mechanisms of genome evolution and is frequently subject to multiple layers of regulation derived from a plethora of environmental and physiological stimuli. Here, we present a regulatory mechanism that illustrates how such disparate stimuli can be integrated into the Streptococcus mutans natural competence phenotype. S. mutans possesses an intriguing, but poorly understood ability to coordinately control its independently regulated natural competence and bacteriocin genetic pathways as a means to acquire DNA released from closely related, bacteriocin-susceptible streptococci. Our results reveal how the bacteriocin-specific transcription activator BrsR directly mediates this coordination by serving as an anti-adaptor protein responsible for antagonizing the proteolysis of the inherently unstable, natural competence-specific alternative sigma factor ComX. This BrsR ability functions entirely independent of its transcription regulator function and directly modulates the timing and severity of the natural competence phenotype. Additionally, many of the DNA uptake proteins produced by the competence system were surprisingly found to possess adaptor abilities, which are employed to terminate the BrsR regulatory circuit via negative feedback. BrsR–competence protein heteromeric complexes directly inhibit nascent brsR transcription as well as stimulate the Clp-dependent proteolysis of extant BrsR proteins. This study illustrates how critical genetic regulatory abilities can evolve in a potentially limitless variety of proteins without disrupting their conserved ancestral functions. These unrecognized regulatory abilities are likely fundamental for transducing information through complex genetic networks.

scholarly journals A transcriptional regulatory circuit for the photosynthetic acclimation of microalgae to carbon dioxide limitation

2020 ◽  
Author(s):  
Olga Blifernez-Klassen ◽  
Hanna Berger ◽  
Birgit Gerlinde Katharina Mittmann ◽  
Viktor Klassen ◽  
Louise Schelletter ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Protein Interactions ◽  
Prolonged Exposure ◽  
Light Harvesting ◽  
Low Carbon ◽  
Protein Protein Interactions ◽  
Regulatory Circuit ◽  
Expression Of Genes ◽  
Transcriptional Regulatory ◽  
Squamosa Promoter Binding Protein

ABSTRACTIn green microalgae, prolonged exposure to inorganic carbon depletion requires long-term acclimation responses, based on a modulated expression of genes and adjusting photosynthetic activity to the prevailing supply of carbon dioxide. Here, we depict a microalgal regulatory cycle, adjusting the light-harvesting capacity at PSII to the prevailing supply of carbon dioxide in Chlamydomonas reinhardtii. It engages a newly identified low carbon dioxide response factor (LCRF), which belongs to the Squamosa promoter binding protein (SBP) family of transcription factors, and the previously characterized cytosolic translation repressor NAB1. LCRF combines a DNA-binding SBP domain with a conserved domain for protein-protein interactions and transcription of the LCRF gene is rapidly induced by carbon dioxide depletion. LCRF activates transcription of the NAB1 gene by specifically binding to tetranucleotide motifs present in its promoter. Accumulation of the NAB1 protein enhances translational repression of its prime target mRNA, encoding the PSII-associated major light-harvesting protein LHCBM6. The resulting reduction of the PSII antenna size helps maintaining a low excitation during the prevailing carbon dioxide limitation. Analyses of low carbon dioxide acclimation in nuclear insertion mutants devoid of a functional LCRF gene confirm the essentiality of this novel transcription factor for the regulatory circuit.

scholarly journals APPL1 is a multifunctional endosomal signaling adaptor protein

2017 ◽  
Vol 45 (3) ◽  
pp. 771-779 ◽  
Author(s):  
Nicole L. Diggins ◽  
Donna J. Webb
Keyword(s):  
Signaling Pathways ◽  
Protein Interactions ◽  
Leucine Zipper ◽  
Adaptor Protein ◽  
Adaptor Proteins ◽  
Ph Domain ◽  
Protein Protein Interactions ◽  
Multiple Protein ◽  
Signaling Receptors ◽  
Ptb Domain

Endosomal adaptor proteins are important regulators of signaling pathways underlying many biological processes. These adaptors can integrate signals from multiple pathways via localization to specific endosomal compartments, as well as through multiple protein–protein interactions. One such adaptor protein that has been implicated in regulating signaling pathways is the adaptor protein containing a pleckstrin homology (PH) domain, phosphotyrosine-binding (PTB) domain, and leucine zipper motif 1 (APPL1). APPL1 localizes to a subset of Rab5-positive endosomes through its Bin–Amphiphysin–Rvs and PH domains, and it coordinates signaling pathways through its interaction with many signaling receptors and proteins through its PTB domain. This review discusses our current understanding of the role of APPL1 in signaling and trafficking, as well as highlights recent work into the function of APPL1 in cell migration and adhesion.

scholarly journals Protein-protein interactions with fructose-1-kinase alter function of the centralEscherichia colitranscription regulator, Cra

2017 ◽  
Author(s):  
Dipika Singh ◽  
Max S. Fairlamb ◽  
Kelly S. Harrison ◽  
Chamitha Weeramange ◽  
Sarah Meinhardt ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Citric Acid Cycle ◽  
Central Metabolism ◽  
Protein Protein Interactions ◽  
Dynamic Regulation ◽  
Acid Cycle ◽  
E Coli ◽  
Transcription Regulator ◽  
Genes Encoding ◽  
Fructose 1,6 Bisphosphate

SummaryInE. coli, the master transcription regulator Cra regulates >100 genes in central metabolism by binding upstream DNA operator sequences. Genes encoding glycolytic enzymes are repressed, whereas those for gluconeogenesis and the citric acid cycle are activated. Cra-DNA binding is allosterically diminished by binding to either fructose-1-phosphate (F-1-P, generated upon fructose import) or fructose-1,6-bisphosphate (F-1,6-BP). F-1,6-BP is generated from F-1-P by the enzyme fructose-1-kinase (FruK) or from other sugars and is a key intermediate in glycolysis. Here, we report that Cra directly interacts with FruK to form a tight protein-protein complex. Further, growth assays with afruKknockout strain show that FruK has a broader role in metabolism than its known role in fructose catabolism. Biochemical experiments show that F-1,6-BP binding enhances either the Cra/FruK interaction and/or CRA binding to DNA and that FruK can catalyze the reverse reaction of F-1,6-BP to F-1-P. Results were used to propose a model in which the Cra-FruK complex enhances activation of gluconeogenic genes. Finally, since FruK itself is repressed by Cra, these newly-reported events add layers to the dynamic regulation ofE. colicentral metabolism that occur in response to changing nutrients.

scholarly journals Protein-protein interactions on membrane surfaces analysed using SUPER template pull-downs

2021 ◽  
Author(s):  
Devika S. Andhare ◽  
Thomas J. Pucadyil
Keyword(s):  
Protein Interactions ◽  
Protein Complexes ◽  
Membrane Surface ◽  
Adaptor Protein ◽  
Protein Protein Interactions ◽  
Membrane Surfaces

AbstractDiscovery-based proteomics workflows that identify novel interactors rely on immunoprecipitations or pull-downs with genetically-tagged bait proteins displayed on sepharose matrices. But strategies to analyse protein interactions on a diffusible membrane surface combined with the practical ease of pull-downs remain unavailable. Such strategies are important to analyse protein complexes that mature in composition and stability because of diffusion-based interactions between participant proteins. Here, we describe a generic pull-down strategy to analyse such complexes using supported membranes with excess reservoir templates displaying His-tagged bait proteins. Using clathrin-mediated endocytosis as a paradigm, we find that the clathrin-binding adaptor protein epsin1 displayed as bait on these templates pulls down significantly higher amounts of clathrin from brain lysates than conventional sepharose matrices. Together, our results establish the potential of SUPER templates as superior matrices for analysing protein-protein interactions and resultant complexes formed on membrane surfaces.

scholarly journals PINCH1 Plays an Essential Role in Early Murine Embryonic Development but Is Dispensable in Ventricular Cardiomyocytes

2005 ◽  
Vol 25 (8) ◽  
pp. 3056-3062 ◽  
Author(s):  
Xingqun Liang ◽  
Qiang Zhou ◽  
Xiaodong Li ◽  
Yunfu Sun ◽  
Min Lu ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Protein Interactions ◽  
Essential Role ◽  
Adaptor Protein ◽  
Protein Protein Interactions ◽  
Signaling Complex ◽  
Basal Phenotype ◽  
Lim Domains ◽  
Ventricular Cardiomyocytes ◽  
Integrin Linked Kinase

ABSTRACT PINCH1, an adaptor protein composed of five LIM domains, mediates protein-protein interactions and functions as a component of the integrin-integrin-linked kinase (ILK) complex. The integrin-ILK signaling complex plays a pivotal role in cell motility, proliferation, and survival during embryonic development of many animal species. To elucidate the physiological function of PINCH1 in mouse embryonic development, we have deleted the mouse PINCH1 gene by homologous recombination. Mice heterozygous for PINCH1 are viable and indistinguishable from wild-type littermates. However, no viable homozygous offspring were observed from PINCH1 +/ − intercrosses. Histological analysis of homozygous mutant embryos revealed that they had a disorganized egg cylinder by E5.5, which degenerated by E6.5. Furthermore, E5.5 PINCH1 − / − embryos exhibited decreased cell proliferation and excessive cell death. We have also generated and analyzed mice in which PINCH1 has been specifically deleted in ventricular cardiomyocytes. These mice exhibit no basal phenotype, with respect to mouse survival, cardiac histology, or cardiac function as measured by echocardiography. Altogether, these data indicate that PINCH1 plays an essential role in early murine embryonic development but is dispensable in ventricular cardiomyocytes.

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