Growth of the Stress-Bearing and Shape-Maintaining Murein Sacculus of Escherichia coli

SUMMARY To withstand the high intracellular pressure, the cell wall of most bacteria is stabilized by a unique cross-linked biopolymer called murein or peptidoglycan. It is made of glycan strands [poly-(GlcNAc-MurNAc)], which are linked by short peptides to form a covalently closed net. Completely surrounding the cell, the murein represents a kind of bacterial exoskeleton known as the murein sacculus. Not only does the sacculus endow bacteria with mechanical stability, but in addition it maintains the specific shape of the cell. Enlargement and division of the murein sacculus is a prerequisite for growth of the bacterium. Two groups of enzymes, hydrolases and synthases, have to cooperate to allow the insertion of new subunits into the murein net. The action of these enzymes must be well coordinated to guarantee growth of the stress-bearing sacculus without risking bacteriolysis. Protein-protein interaction studies suggest that this is accomplished by the formation of a multienzyme complex, a murein-synthesizing machinery combining murein hydrolases and synthases. Enlargement of both the multilayered murein of gram-positive and the thin, single-layered murein of gram-negative bacteria seems to follow an inside-to-outside growth strategy. New material is hooked in a relaxed state underneath the stress-bearing sacculus before it becomes inserted upon cleavage of covalent bonds in the layer(s) under tension. A model is presented that postulates that maintenance of bacterial shape is achieved by the enzyme complex copying the preexisting murein sacculus that plays the role of a template.

Download Full-text

POPDC proteins and cardiac function

Biochemical Society Transactions ◽

10.1042/bst20190249 ◽

2019 ◽

Vol 47 (5) ◽

pp. 1393-1404 ◽

Cited By ~ 4

Author(s):

Thomas Brand

Keyword(s):

Potential Role ◽

Striated Muscle ◽

Short Review ◽

Effector Proteins ◽

Muscle Disease ◽

Disease Genes ◽

Protein Protein Interaction ◽

Interaction Partners ◽

And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

Download Full-text

Beckett's Broken Circle: A Literary Fractal

Journal of Beckett Studies ◽

10.3366/jobs.2020.0311 ◽

2020 ◽

Vol 29 (2) ◽

pp. 196-215

Author(s):

Luke Connolly

Keyword(s):

Dynamic Chaos ◽

Geometric Form ◽

Self Similarity ◽

Collision Point ◽

Stable Order ◽

Structural Principle ◽

Recent Interest ◽

Viable Solution ◽

Specific Shape

This essay proposes that the picture of a broken circle encountered by Watt during the second part of his tale marks a crucial collision point between Beckett's literary and mathematical interests and triggers a process of fractal scaling self-similarity. Building on recent interest concerning the role of the mathematics and mathematical forms found in Beckett's work, I argue that the broken circle depicted in the picture from Watt is a geometric form which (re)appears within at least three interlocking scales throughout Beckett's novel-length prose: (i) its moment of arrival in the picture from Watt, (ii) a macroscopic reinscription in the names of the protagonists populating the five novels spanning Watt through to The Unnamable and (iii) buried within the narratological depths of How It Is. As a structural principle, the interminable irregularity of fractals offered Beckett a viable solution for what he considered the defining task of the modern artist: ‘to find a form to accommodate the mess’. Moreover, the specific shape selected for his fractal is shown to contain within its geometry one of Beckett's most universal and pressing concerns: the inevitable insufficiency of language. Therefore, although this essay restricts itself to examining Beckett's novel-length prose, the idea of a broken circle fractal promises to provide a valuable heuristic through which to reassess the author's other generic avenues. Fractals thus offer a means through which one can bind together the length and breadth of Beckett's oeuvre without ever reducing dynamic chaos to stable order.

Download Full-text

Genome-wide identification of the GATA transcription factor family and their expression patterns under temperature and salt stress in Aspergillus oryzae

AMB Express ◽

10.1186/s13568-021-01212-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Chunmiao Jiang ◽

Gongbo Lv ◽

Jinxin Ge ◽

Bin He ◽

Zhe Zhang ◽

...

Keyword(s):

Salt Stress ◽

Expression Patterns ◽

Interaction Network ◽

Protein Protein Interaction ◽

Genome Wide ◽

Gata Transcription Factor ◽

Starting Point ◽

Evolutionary Features ◽

First Time

AbstractGATA transcription factors (TFs) are involved in the regulation of growth processes and various environmental stresses. Although GATA TFs involved in abiotic stress in plants and some fungi have been analyzed, information regarding GATA TFs in Aspergillusoryzae is extremely poor. In this study, we identified and functionally characterized seven GATA proteins from A.oryzae 3.042 genome, including a novel AoSnf5 GATA TF with 20-residue between the Cys-X2-Cys motifs which was found in Aspergillus GATA TFs for the first time. Phylogenetic analysis indicated that these seven A. oryzae GATA TFs could be classified into six subgroups. Analysis of conserved motifs demonstrated that Aspergillus GATA TFs with similar motif compositions clustered in one subgroup, suggesting that they might possess similar genetic functions, further confirming the accuracy of the phylogenetic relationship. Furthermore, the expression patterns of seven A.oryzae GATA TFs under temperature and salt stresses indicated that A. oryzae GATA TFs were mainly responsive to high temperature and high salt stress. The protein–protein interaction network of A.oryzae GATA TFs revealed certain potentially interacting proteins. The comprehensive analysis of A. oryzae GATA TFs will be beneficial for understanding their biological function and evolutionary features and provide an important starting point to further understand the role of GATA TFs in the regulation of distinct environmental conditions in A.oryzae.

Download Full-text

MexAB-OprM Efflux Pump Interaction with the Peptidoglycan of Escherichia coli and Pseudomonas aeruginosa

International Journal of Molecular Sciences ◽

10.3390/ijms22105328 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5328

Author(s):

Miao Ma ◽

Margaux Lustig ◽

Michèle Salem ◽

Dominique Mengin-Lecreulx ◽

Gilles Phan ◽

...

Keyword(s):

Escherichia Coli ◽

Pseudomonas Aeruginosa ◽

Cell Division ◽

Membrane Proteins ◽

Outer Membrane ◽

Efflux Pump ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Active Efflux

One of the major families of membrane proteins found in prokaryote genome corresponds to the transporters. Among them, the resistance-nodulation-cell division (RND) transporters are highly studied, as being responsible for one of the most problematic mechanisms used by bacteria to resist to antibiotics, i.e., the active efflux of drugs. In Gram-negative bacteria, these proteins are inserted in the inner membrane and form a tripartite assembly with an outer membrane factor and a periplasmic linker in order to cross the two membranes to expulse molecules outside of the cell. A lot of information has been collected to understand the functional mechanism of these pumps, especially with AcrAB-TolC from Escherichia coli, but one missing piece from all the suggested models is the role of peptidoglycan in the assembly. Here, by pull-down experiments with purified peptidoglycans, we precise the MexAB-OprM interaction with the peptidoglycan from Escherichia coli and Pseudomonas aeruginosa, highlighting a role of the peptidoglycan in stabilizing the MexA-OprM complex and also differences between the two Gram-negative bacteria peptidoglycans.

Download Full-text

Connecting the αα-hubs: same fold, disordered ligands, new functions

Cell Communication and Signaling ◽

10.1186/s12964-020-00686-8 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Lasse Staby ◽

Katrine Bugge ◽

Rasmus Greve Falbe-Hansen ◽

Edoardo Salladini ◽

Karen Skriver ◽

...

Keyword(s):

Intrinsically Disordered Proteins ◽

Disordered Proteins ◽

Telomere Elongation ◽

Protein Protein Interaction ◽

Intrinsically Disordered ◽

Functional Understanding ◽

Signal Specificity ◽

Telomere Regulation ◽

Secondary Structure Motif

Abstract Background Signal fidelity depends on protein–protein interaction–‘hubs’ integrating cues from large interactomes. Recently, and based on a common secondary structure motif, the αα-hubs were defined, which are small α-helical domains of large, modular proteins binding intrinsically disordered transcriptional regulators. Methods Comparative structural biology. Results We assign the harmonin-homology-domain (HHD, also named the harmonin N-terminal domain, NTD) present in large proteins such as harmonin, whirlin, cerebral cavernous malformation 2, and regulator of telomere elongation 1 to the αα-hubs. The new member of the αα-hubs expands functionality to include scaffolding of supra-modular complexes mediating sensory perception, neurovascular integrity and telomere regulation, and reveal novel features of the αα-hubs. As a common trait, the αα-hubs bind intrinsically disordered ligands of similar properties integrating similar cellular cues, but without cross-talk. Conclusion The inclusion of the HHD in the αα-hubs has uncovered new features, exemplifying the utility of identifying groups of hub domains, whereby discoveries in one member may cross-fertilize discoveries in others. These features make the αα-hubs unique models for decomposing signal specificity and fidelity. Using these as models, together with other suitable hub domain, we may advance the functional understanding of hub proteins and their role in cellular communication and signaling, as well as the role of intrinsically disordered proteins in signaling networks.

Download Full-text

Roadmap for Stroke: Challenging the Role of the Neuronal Extracellular Matrix

International Journal of Molecular Sciences ◽

10.3390/ijms21207554 ◽

2020 ◽

Vol 21 (20) ◽

pp. 7554

Author(s):

Ciro De Luca ◽

Assunta Virtuoso ◽

Nicola Maggio ◽

Sara Izzo ◽

Michele Papa ◽

...

Keyword(s):

Extracellular Matrix ◽

Inflammatory Response ◽

Neurovascular Unit ◽

Neuronal Loss ◽

Modern Medicine ◽

Metabolic Demand ◽

Protein Protein Interaction ◽

Stroke Research ◽

Accurate Design

Stroke is a major challenge in modern medicine and understanding the role of the neuronal extracellular matrix (NECM) in its pathophysiology is fundamental for promoting brain repair. Currently, stroke research is focused on the neurovascular unit (NVU). Impairment of the NVU leads to neuronal loss through post-ischemic and reperfusion injuries, as well as coagulatory and inflammatory processes. The ictal core is produced in a few minutes by the high metabolic demand of the central nervous system. Uncontrolled or prolonged inflammatory response is characterized by leukocyte infiltration of the injured site that is limited by astroglial reaction. The metabolic failure reshapes the NECM through matrix metalloproteinases (MMPs) and novel deposition of structural proteins continues within months of the acute event. These maladaptive reparative processes are responsible for the neurological clinical phenotype. In this review, we aim to provide a systems biology approach to stroke pathophysiology, relating the injury to the NVU with the pervasive metabolic failure, inflammatory response and modifications of the NECM. The available data will be used to build a protein–protein interaction (PPI) map starting with 38 proteins involved in stroke pathophysiology, taking into account the timeline of damage and the co-expression scores of their RNA patterns The application of the proposed network could lead to a more accurate design of translational experiments aiming at improving both the therapy and the rehabilitation processes.

Download Full-text

Regulation of clathrin coat assembly by Eps15 homology domain–mediated interactions during endocytosis

Molecular Biology of the Cell ◽

10.1091/mbc.e11-04-0380 ◽

2012 ◽

Vol 23 (4) ◽

pp. 687-700 ◽

Cited By ~ 7

Author(s):

Ryohei Suzuki ◽

Junko Y. Toshima ◽

Jiro Toshima

Keyword(s):

Functional Diversity ◽

Protein Interaction ◽

Interaction Domain ◽

Protein Protein Interaction ◽

Molecular Events ◽

Biological Studies ◽

Eh Domain ◽

Actin Patch ◽

Lines Of Evidence

Clathrin-mediated endocytosis involves a coordinated series of molecular events regulated by interactions among a variety of proteins and lipids through specific domains. One such domain is the Eps15 homology (EH) domain, a highly conserved protein–protein interaction domain present in a number of proteins distributed from yeast to mammals. Several lines of evidence suggest that the yeast EH domain–containing proteins Pan1p, End3p, and Ede1p play important roles during endocytosis. Although genetic and cell-biological studies of these proteins suggested a role for the EH domains in clathrin-mediated endocytosis, it was unclear how they regulate clathrin coat assembly. To explore the role of the EH domain in yeast endocytosis, we mutated those of Pan1p, End3p, or Ede1p, respectively, and examined the effects of single, double, or triple mutation on clathrin coat assembly. We found that mutations of the EH domain caused a defect of cargo internalization and a delay of clathrin coat assembly but had no effect on assembly of the actin patch. We also demonstrated functional redundancy among the EH domains of Pan1p, End3p, and Ede1p for endocytosis. Of interest, the dynamics of several endocytic proteins were differentially affected by various EH domain mutations, suggesting functional diversity of each EH domain.

Download Full-text

DNA methylation in Yersinia enterocolitica: role of the DNA adenine methyltransferase in mismatch repair and regulation of virulence factors

Microbiology ◽

10.1099/mic.0.27946-0 ◽

2005 ◽

Vol 151 (7) ◽

pp. 2291-2299 ◽

Cited By ~ 21

Author(s):

Stefan Fälker ◽

M. Alexander Schmidt ◽

Gerhard Heusipp

Keyword(s):

Mismatch Repair ◽

Yersinia Enterocolitica ◽

Virulence Genes ◽

Spontaneous Mutation ◽

Gram Negative Bacteria ◽

E Coli ◽

Physiological Processes ◽

Dna Adenine Methyltransferase

DNA adenine methyltransferase (Dam) plays an important role in physiological processes of Gram-negative bacteria such as mismatch repair and replication. In addition, Dam regulates the expression of virulence genes in various species. The authors cloned the dam gene of Yersinia enterocolitica and showed that Dam is essential for viability. Dam overproduction in Y. enterocolitica resulted in an increased frequency of spontaneous mutation and decreased resistance to 2-aminopurine; however, these effects were only marginal compared to the effect of overproduction of Escherichia coli-derived Dam in Y. enterocolitica, implying different roles or activities of Dam in mismatch repair of the two species. These differences in Dam function are not the cause for the essentiality of Dam in Y. enterocolitica, as Dam of E. coli can complement a dam defect in Y. enterocolitica. Instead, Dam seems to interfere with expression of essential genes. Furthermore, Dam mediates virulence of Y. enterocolitica. Dam overproduction results in increased tissue culture invasion of Y. enterocolitica, while the expression of specifically in vivo-expressed genes is not altered.

Download Full-text