scholarly journals Conserved architecture of Tc toxins from human and insect pathogenic bacteria

2019 ◽  
Author(s):  
Franziska Leidreiter ◽  
Daniel Roderer ◽  
Dominic Meusch ◽  
Christos Gatsogiannis ◽  
Roland Benz ◽  
...  
Keyword(s):  
High Resolution ◽  
Host Specificity ◽  
Mechanism Of Action ◽  
Pathogenic Bacteria ◽  
Structural Features ◽  
Common Mechanism ◽  
Ionic Pair ◽  
Domain Organization ◽  
Functional Studies ◽  
Β Sheet

AbstractTc toxin complexes use a syringe-like mechanism to penetrate the membrane and translocate a toxic enzyme into the host cytosol. They are composed of three components: TcA, TcB and TcC. Until recently, low-resolution structures of TcA from different bacteria suggested that Tc toxins differ considerably in their architecture and possibly in their mechanism of action. Here, we present high-resolution structures and functional studies of five TcAs from different insect and human pathogenic bacteria. Contrary to previous expectations, their overall composition and domain organization is almost identical. The TcAs assemble as a pentamer with a central α-helical channel surrounded by a shell composed of conserved α-helical domains and variable β-sheet domains. Essential structural features, including a conserved trefoil protein knot, are present in all five TcAs, suggesting a common mechanism of action. All TcAs form functional pores and can be combined with TcB-TcC subunits from other species resulting in chimeric holotoxins. We have identified a conserved ionic pair that stabilizes the shell, likely operating as a strong latch that only springs open after the destabilization of other regions. Our results lead to new insights into the architecture and host specificity of the Tc toxin family.

scholarly journals Common architecture of Tc toxins from human and insect pathogenic bacteria

2019 ◽  
Vol 5 (10) ◽  
pp. eaax6497 ◽  
Author(s):  
F. Leidreiter ◽  
D. Roderer ◽  
D. Meusch ◽  
C. Gatsogiannis ◽  
R. Benz ◽  
...  
Keyword(s):  
High Resolution ◽  
Mechanism Of Action ◽  
Pathogenic Bacteria ◽  
Structural Features ◽  
Common Mechanism ◽  
Ionic Pair ◽  
Human Pathogens ◽  
Low Resolution ◽  
Domain Organization ◽  
Common Architecture

Tc toxins use a syringe-like mechanism to penetrate the membrane and translocate toxic enzymes into the host cytosol. They are composed of three components: TcA, TcB, and TcC. Low-resolution structures of TcAs from different bacteria suggest a considerable difference in their architecture and possibly in their mechanism of action. Here, we present high-resolution structures of five TcAs from insect and human pathogens, which show a similar overall composition and domain organization. Essential structural features, including a trefoil protein knot, are present in all TcAs, suggesting a common mechanism of action. All TcAs form functional pores and can be combined with TcB-TcC subunits from other species to form active chimeric holotoxins. We identified a conserved ionic pair that stabilizes the shell, likely operating as a strong latch that only springs open after destabilization of other regions. Our results provide new insights into the architecture and mechanism of the Tc toxin family.

Skeletal elements of crinoid echinoderms: High-resolution structural and microanalytical results

1983 ◽  
Vol 41 ◽  
pp. 194-195
Author(s):  
D. F. Blake ◽  
L. F. Allard ◽  
D. R. Peacor
Keyword(s):  
High Resolution ◽  
Marine Invertebrates ◽  
Sea Urchins ◽  
Structural Features ◽  
Sea Stars ◽  
High Resolution Tem ◽  
Relationship Of ◽  
The Relationship ◽  
Insight Into

Echinodermata is a phylum of marine invertebrates which has been extant since Cambrian time (c.a. 500 m.y. before the present). Modern examples of echinoderms include sea urchins, sea stars, and sea lilies (crinoids). The endoskeletons of echinoderms are composed of plates or ossicles (Fig. 1) which are with few exceptions, porous, single crystals of high-magnesian calcite. Despite their single crystal nature, fracture surfaces do not exhibit the near-perfect {10.4} cleavage characteristic of inorganic calcite. This paradoxical mix of biogenic and inorganic features has prompted much recent work on echinoderm skeletal crystallography. Furthermore, fossil echinoderm hard parts comprise a volumetrically significant portion of some marine limestones sequences. The ultrastructural and microchemical characterization of modern skeletal material should lend insight into: 1). The nature of the biogenic processes involved, for example, the relationship of Mg heterogeneity to morphological and structural features in modern echinoderm material, and 2). The nature of the diagenetic changes undergone by their ancient, fossilized counterparts. In this study, high resolution TEM (HRTEM), high voltage TEM (HVTEM), and STEM microanalysis are used to characterize tha ultrastructural and microchemical composition of skeletal elements of the modern crinoid Neocrinus blakei.

Cytosolic protein quality control machinery: Interactions of Hsp70 with a network of co-chaperones and substrates

2021 ◽  
pp. 153537022199981
Author(s):  
Chamithi Karunanayake ◽  
Richard C Page
Keyword(s):  
Quality Control ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Structural Features ◽  
Cellular Protein ◽  
Mechanisms Of Action ◽  
Control Mechanisms ◽  
Nucleotide Exchange ◽  
Domain Organization ◽  
Nucleotide Exchange Factors

The chaperone heat shock protein 70 (Hsp70) and its network of co-chaperones serve as a central hub of cellular protein quality control mechanisms. Domain organization in Hsp70 dictates ATPase activity, ATP dependent allosteric regulation, client/substrate binding and release, and interactions with co-chaperones. The protein quality control activities of Hsp70 are classified as foldase, holdase, and disaggregase activities. Co-chaperones directly assisting protein refolding included J domain proteins and nucleotide exchange factors. However, co-chaperones can also be grouped and explored based on which domain of Hsp70 they interact. Here we discuss how the network of cytosolic co-chaperones for Hsp70 contributes to the functions of Hsp70 while closely looking at their structural features. Comparison of domain organization and the structures of co-chaperones enables greater understanding of the interactions, mechanisms of action, and roles played in protein quality control.

scholarly journals Bacteriophage-derived CHAP domain protein, P128, kills Staphylococcus cells by cleaving interpeptide cross-bridge of peptidoglycan

Microbiology ◽  
2014 ◽  
Vol 160 (10) ◽  
pp. 2157-2169 ◽  
Author(s):  
Sudarson Sundarrajan ◽  
Junjappa Raghupatil ◽  
Aradhana Vipra ◽  
Nagalakshmi Narasimhaswamy ◽  
Sanjeev Saravanan ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Mechanism Of Action ◽  
Catalytic Domain ◽  
Antibiotic Sensitivity ◽  
High Sensitivity ◽  
Common Mechanism ◽  
Cross Bridge ◽  
Sensitivity Pattern

P128 is an anti-staphylococcal protein consisting of the Staphylococcus aureus phage-K-derived tail-associated muralytic enzyme (TAME) catalytic domain (Lys16) fused with the cell-wall-binding SH3b domain of lysostaphin. In order to understand the mechanism of action and emergence of resistance to P128, we isolated mutants of Staphylococcus spp., including meticillin-resistant Staphylococcus aureus (MRSA), resistant to P128. In addition to P128, the mutants also showed resistance to Lys16, the catalytic domain of P128. The mutants showed loss of fitness as shown by reduced rate of growth in vitro. One of the mutants tested was found to show reduced virulence in animal models of S. aureus septicaemia suggesting loss of fitness in vivo as well. Analysis of the antibiotic sensitivity pattern showed that the mutants derived from MRSA strains had become sensitive to meticillin and other β-lactams. Interestingly, the mutant cells were resistant to the lytic action of phage K, although the phage was able to adsorb to these cells. Sequencing of the femA gene of three P128-resistant mutants showed either a truncation or deletion in femA, suggesting that improper cross-bridge formation in S. aureus could be causing resistance to P128. Using glutathione S-transferase (GST) fusion peptides as substrates it was found that both P128 and Lys16 were capable of cleaving a pentaglycine sequence, suggesting that P128 might be killing S. aureus by cleaving the pentaglycine cross-bridge of peptidoglycan. Moreover, peptides corresponding to the reported cross-bridge of Staphylococcus haemolyticus (GGSGG, AGSGG), which were not cleaved by lysostaphin, were cleaved efficiently by P128. This was also reflected in high sensitivity of S. haemolyticus to P128. This showed that in spite of sharing a common mechanism of action with lysostaphin, P128 has unique properties, which allow it to act on certain lysostaphin-resistant Staphylococcus strains.

Volcanoes geological mapping and structural geology with UAS High Resolution Digital Terrain Model : the Kuei-Shan Tao case example (Eastern Taiwan).

2021 ◽  
Author(s):  
Benoit Deffontaines ◽  
Kuo-Jen Chang ◽  
Samuel Magalhaes ◽  
Gérardo Fortunato
Keyword(s):  
High Resolution ◽  
Okinawa Trough ◽  
Volcanic Rocks ◽  
Digital Terrain Model ◽  
Structural Features ◽  
Point Of View ◽  
Geological Mapping ◽  
Lava Flows ◽  
Aerial Photographs ◽  
Structural Scheme

<p>Volcanic areas in the World are often difficult to map especially in a structural point of view as (1) fault planes are generally covered and filled by more recent lava flows and (2) volcanic rocks have very few tectonic striations. Kuei-Shan Tao (11km from Ilan Plain – NE Taiwan) is a volcanic island, located at the soutwestern tip of the South Okinawa trough (SWOT). Two incompatible geological maps had been already published both lacking faults and structural features (Hsu, 1963 and Chiu et al., 2010). We propose herein not only to up-date the Kuei-Shan Tao geological map with our high resolution dataset, but also to create the Kuei-Shan Tao structural scheme in order to better understand its geological and tectonic history.</p><p>Consequently, we first acquired aerial photographs from our UAS survey and get our new UAS high resolution DTM (HR UAS-DTM hereafter) with a ground resolution <10cm processed through classical photogrammetric methods. Taking into account common sense geomorphic and structural interpretation and reasoning deduced form our HR UAS-DTM, and the outcropping lithologies situated all along the shoreline, we have up-dated the Kuei-Shan Tao geological mapping and its major structures. To conclude, the lithologies (andesitic lava flows and pyroclastic falls) and the new structural scheme lead us to propose a scenario for both the construction as well as the dismantling of Kuei-Shan Tao which are keys for both geology and geodynamics of the SWOT.</p>

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