scholarly journals What is the role of lipid membrane-embedded quinones in ATP-synthesis? Chemiosmotic Q-cycle versus murburn reaction perspective

2020 ◽  
Author(s):  
Kelath Murali Manoj ◽  
Daniel Andrew Gideon ◽  
Abhinav Parashar
Keyword(s):  
Lipid Membranes ◽  
Lipid Membrane ◽  
Protein Complexes ◽  
Atp Synthesis ◽  
Structural Features ◽  
E Coli ◽  
Q Cycle ◽  
Transport Chain ◽  
Associated Proteins

Quinones are found in the lipid-membranes of prokaryotes like E. coli and cyanobacteria, and are also abundant in eukaryotic mitochondria and chloroplasts. They are intricately involved in the reaction mechanism of redox phosphorylations. In the Mitchellian chemiosmotic school of thought, membrane-lodged quinones are perceived as highly mobile conveyors of two-electron equivalents from the first leg of Electron Transport Chain (ETC) to the ‘second pit-stop’ of Cytochrome bc1 or b6f complex (CBC), where they undergo a regenerative ‘Q-cycle’. In Manoj’s murburn mechanism, the membrane-lodged quinones are perceived as one- or two- electron donors/acceptors, enabling charge separation and the CBC resets a one-electron paradigm via ‘turbo logic’. Herein, we compare various purviews of the two mechanistic schools with respect to: constraints in mobility, protons’ availability, binding of quinones with proteins, structural features of the protein complexes, energetics of reaction, overall reaction logic, etc. From various perspectives, it is concluded that the chemiosmotic Q-cycle is an untenable hypothesis. We project the murburn proposal as one rooted in thermodynamics/kinetics and which provides tangible structure-function correlations for the roles of quinones, lipid membrane and associated proteins.

scholarly journals Mitochondrial microRNAs: A Putative Role in Tissue Regeneration

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 486
Author(s):  
Sílvia C. Rodrigues ◽  
Renato M. S. Cardoso ◽  
Filipe V. Duarte
Keyword(s):  
Tissue Regeneration ◽  
Protein Complexes ◽  
Mitochondrial Protein ◽  
Noncoding Rnas ◽  
Atp Synthesis ◽  
Mitochondrial Proteins ◽  
Cellular Mechanisms ◽  
Small Noncoding Rnas ◽  
Mitochondrial Ribosome

The most famous role of mitochondria is to generate ATP through oxidative phosphorylation, a metabolic pathway that involves a chain of four protein complexes (the electron transport chain, ETC) that generates a proton-motive force that in turn drives the ATP synthesis by the Complex V (ATP synthase). An impressive number of more than 1000 mitochondrial proteins have been discovered. Since mitochondrial proteins have a dual genetic origin, it is predicted that ~99% of these proteins are nuclear-encoded and are synthesized in the cytoplasmatic compartment, being further imported through mitochondrial membrane transporters. The lasting 1% of mitochondrial proteins are encoded by the mitochondrial genome and synthesized by the mitochondrial ribosome (mitoribosome). As a result, an appropriate regulation of mitochondrial protein synthesis is absolutely required to achieve and maintain normal mitochondrial function. Regarding miRNAs in mitochondria, it is well-recognized nowadays that several cellular mechanisms involving mitochondria are regulated by many genetic players that originate from either nuclear- or mitochondrial-encoded small noncoding RNAs (sncRNAs). Growing evidence collected from whole genome and transcriptome sequencing highlight the role of distinct members of this class, from short interfering RNAs (siRNAs) to miRNAs and long noncoding RNAs (lncRNAs). Some of the mechanisms that have been shown to be modulated are the expression of mitochondrial proteins itself, as well as the more complex coordination of mitochondrial structure and dynamics with its function. We devote particular attention to the role of mitochondrial miRNAs and to their role in the modulation of several molecular processes that could ultimately contribute to tissue regeneration accomplishment.

scholarly journals Direct and indirect interactions promote complexes of the lipoprotein LbcA, the CtpA protease and its substrates, and other cell wall proteins in Pseudomonas aeruginosa

2021 ◽  
Author(s):  
Dolonchapa Chakraborty ◽  
Andrew J. Darwin
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Cell Wall ◽  
Protein Complexes ◽  
Associated Proteins ◽  
Carboxyl Terminal ◽  
Multiple Species ◽  
Processing Protease ◽  
Enzyme Complexes

The Pseudomonas aeruginosa lipoprotein LbcA was discovered because it copurified with and promoted the activity of CtpA, a carboxyl-terminal processing protease (CTP) required for type III secretion system function, and for virulence in a mouse model of acute pneumonia. In this study we explored the role of LbcA by determining its effect on the proteome and its participation in protein complexes. lbcA and ctpA null mutations had strikingly similar effects on the proteome, suggesting that assisting CtpA might be the most impactful role of LbcA in the bacterial cell. Independent complexes containing LbcA and CtpA, or LbcA and substrate, were isolated from P. aeruginosa cells, indicating that LbcA facilitates proteolysis by recruiting the protease and its substrates independently. An unbiased examination of proteins that copurified with LbcA revealed an enrichment for proteins associated with the cell wall. One of these copurification partners was found to be a new CtpA substrate, and the first substrate that is not a peptidoglycan hydrolase. Many of the other LbcA copurification partners are known or predicted peptidoglycan hydrolases. However, some of these LbcA copurification partners were not cleaved by CtpA, and an in vitro assay revealed that while CtpA and all of its substrates bound to LbcA directly, these non-substrates did not. Subsequent experiments suggested that the non substrates might co-purify with LbcA by participating in multi-enzyme complexes containing LbcA-binding CtpA substrates. IMPORTANCE Carboxyl-terminal processing proteases (CTPs) are widely conserved and associated with the virulence of several bacteria, including CtpA in Pseudomonas aeruginosa . CtpA copurifies with the uncharacterized lipoprotein, LbcA. This study shows that the most impactful role of LbcA might be to promote CtpA-dependent proteolysis, and that it achieves this as a scaffold for CtpA and its substrates. It also reveals that LbcA copurification partners are enriched for cell wall-associated proteins, one of which is a novel CtpA substrate. Some of the LbcA copurification partners are not cleaved by CtpA, but might copurify with LbcA because they participate in multi-enzyme complexes containing CtpA substrates. These findings are important, because CTPs and their associated proteins affect peptidoglycan remodeling and virulence in multiple species.

scholarly journals Responsive core-shell DNA particles trigger lipid-membrane disruption and bacteria entrapment

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Michal Walczak ◽  
Ryan A. Brady ◽  
Leonardo Mancini ◽  
Claudia Contini ◽  
Roger Rubio-Sánchez ◽  
...  
Keyword(s):  
Immune Cells ◽  
Lipid Membranes ◽  
Lipid Membrane ◽  
Lipid Vesicles ◽  
Membrane Disruption ◽  
Dna Nanostructures ◽  
E Coli ◽  
Synthetic Dna ◽  
Amyloid Aggregates ◽  
Particle Coalescence

AbstractBiology has evolved a variety of agents capable of permeabilizing and disrupting lipid membranes, from amyloid aggregates, to antimicrobial peptides, to venom compounds. While often associated with disease or toxicity, these agents are also central to many biosensing and therapeutic technologies. Here, we introduce a class of synthetic, DNA-based particles capable of disrupting lipid membranes. The particles have finely programmable size, and self-assemble from all-DNA and cholesterol-DNA nanostructures, the latter forming a membrane-adhesive core and the former a protective hydrophilic corona. We show that the corona can be selectively displaced with a molecular cue, exposing the ‘sticky’ core. Unprotected particles adhere to synthetic lipid vesicles, which in turn enhances membrane permeability and leads to vesicle collapse. Furthermore, particle-particle coalescence leads to the formation of gel-like DNA aggregates that envelop surviving vesicles. This response is reminiscent of pathogen immobilisation through immune cells secretion of DNA networks, as we demonstrate by trapping E. coli bacteria.

scholarly journals Insights into glycan import by a prominent gut symbiont

2020 ◽  
Author(s):  
Declan A. Gray ◽  
Joshua B. R. White ◽  
Abraham O. Oluwole ◽  
Parthasarathi Rath ◽  
Amy J. Glenwright ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Transport Mechanism ◽  
Protein Complexes ◽  
Native Mass Spectrometry ◽  
Structural Features ◽  
Titration Calorimetry ◽  
Binding Cavity ◽  
Shed Light

AbstractIn Bacteroidetes, one of the dominant phyla of the mammalian gut, active uptake of large nutrients across the outer membrane is mediated by SusCD protein complexes via a “pedal bin” transport mechanism. However, many features of SusCD function in glycan uptake remain unclear, including ligand binding, the role of the SusD lid and the size limit for substrate transport. Here we characterise the β2,6 fructo-oligosaccharide (FOS) importing SusCD from Bacteroides thetaiotaomicron (Bt1762-Bt1763) to shed light on SusCD function. Co-crystal structures reveal residues involved in glycan recognition and suggest that the large binding cavity can accommodate several substrate molecules, each up to ∼2.5 kDa in size, a finding supported by native mass spectrometry and isothermal titration calorimetry. Mutational studies in vivo provide functional insights into the key structural features of the SusCD apparatus and cryo-EM of the intact dimeric SusCD complex reveals several distinct states of the transporter, directly visualising the dynamics of the pedal bin transport mechanism.

scholarly journals Role-Playing Activity to Demonstrate the Electron Transport Chain

2020 ◽  
Vol 82 (5) ◽  
pp. 338-340
Author(s):  
Elizabeth Harrison
Keyword(s):  
Electron Transport ◽  
Electron Transport Chain ◽  
Cost Effective ◽  
Role Playing ◽  
Introductory Biology ◽  
Single Class ◽  
Biology Students ◽  
Transport Chain ◽  
Associated Proteins

The role of the electron transport chain, its associated proteins, and carrier molecules can be difficult for introductory biology students to understand. Role-playing activities provide a simple, active, cost-effective method for demonstrating and comprehending complex biological processes. This role-playing activity was designed to help introductory biology students learn the role of the electron transport chain in the synthesis of ATP. The activity can be completed within a single class period and, when combined with a post-activity writing assignment, can enhance student understanding of how the electron transport chain functions.

scholarly journals Role of A-type lamins in signaling, transcription, and chromatin organization

2009 ◽  
Vol 187 (7) ◽  
pp. 945-957 ◽  
Author(s):  
Vicente Andrés ◽  
José M. González
Keyword(s):  
Striated Muscle ◽  
Protein Complexes ◽  
Complex Structure ◽  
Nuclear Lamina ◽  
Major Protein ◽  
Progeroid Syndromes ◽  
Neuronal Tissues ◽  
Associated Proteins ◽  
Health And Disease

A-type lamins (lamins A and C), encoded by the LMNA gene, are major protein constituents of the mammalian nuclear lamina, a complex structure that acts as a scaffold for protein complexes that regulate nuclear structure and functions. Interest in these proteins has increased in recent years with the discovery that LMNA mutations cause a variety of human diseases termed laminopathies, including progeroid syndromes and disorders that primarily affect striated muscle, adipose, bone, and neuronal tissues. In this review, we discuss recent research supporting the concept that lamin A/C and associated nuclear envelope proteins regulate gene expression in health and disease through interplay with signal transduction pathways, transcription factors, and chromatin-associated proteins.

scholarly journals The Role of Non-Canonical Hsp70s (Hsp110/Grp170) in Cancer

2020 ◽  
Author(s):  
Graham Chakafana ◽  
Addmore Shonhai
Keyword(s):  
Heat Shock ◽  
Drug Targets ◽  
Structural Features ◽  
Cancer Development ◽  
Fair Share ◽  
E Coli ◽  
Binding Domains ◽  
Current Review ◽  
Shock Proteins

Although cancers account for over 16% of all global deaths annually, at present, no reliable therapies exist for most types of the disease. As protein folding facilitators, heat shock proteins (Hsps) play an important role in cancer development. Not surprisingly, Hsps are among leading anticancer drug targets. Generally, Hsp70s are divided into two main subtypes: canonical Hsp70 (E. coli Hsp70/DnaK homologues) and the non-canonical (Hsp110 and Grp170) members. These two main Hsp70 groups are delineated from each other by distinct structural and functional specifications. Non-canonical Hsp70s are considered as holdase chaperones, while canonical Hsp70s are refoldases. This distinct characteristic feature is mirrored by the distinct structural features of these two groups of chaperones. Hsp110/Grp170 members are larger as they possess an extended acidic insertion in their substrate binding domains. While the role of canonical Hsp70s in cancer has received a fair share of attention, the roles of non-canonical Hsp70s in cancer development has received less attention in comparison. In the current review, we discuss the structure-function features of non-canonical Hsp70s members and how these features impact on their role in cancer development. We further mapped out their interactome and discussed the prospects of targeting these proteins in cancer therapy.

scholarly journals An Abnormally High Closing Potential of the OMPF Porin Channel from Yersinia Ruckeri: The Role of Charged Residues and Intramolecular Bonds

Acta Naturae ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 89-98
Author(s):  
D. K. Chistyulin ◽  
O. D. Novikova ◽  
E. A. Zelepuga ◽  
V. A. Khomenko ◽  
G. N. Likhatskaya ◽  
...  
Keyword(s):  
Lipid Membranes ◽  
Gram Negative Bacteria ◽  
Amino Acid Residues ◽  
Yersinia Ruckeri ◽  
Ompf Porin ◽  
E Coli ◽  
Total Conductance ◽  
Voltage Dependent ◽  
Acidic Conditions

Electrophysiological experiments on bilayer lipid membranes showed that the isolated outer membrane major porin of Yersinia ruckeri (YrOmpF) exhibits activity typical of porins from Gram-negative bacteria, forming channels with a mean conductance of 230 pS (in 0.1 M KCl) and slight asymmetry with respect to the applied voltage. Under acidic conditions (up to pH = 3.0), there was no significant decrease in the total conductance of the YrOmpF channel reconstituted into the bilayer. The studied channel significantly differed from the porins of other bacteria by high values of its critical closing potential (Vc): Vc = 232 mV at pH = 7.0 and Vc = 164 mV at pH = 5.0. A theoretical model of the YrOmpF spatial structure was used for the analysis of the charge distribution in the mouth and inside the channel to explain these properties and quantitatively assess the bonds between the amino acid residues in the L3 loop and on the inner wall of the barrel. The parameters of YrOmpF were compared with those of the classical OmpF porin from E. coli. The results of electrophysiological experiments and theoretical analysis are discussed in terms of the mechanism for voltage-dependent closing of porin channels.

scholarly journals Insights into SusCD-mediated glycan import by a prominent gut symbiont

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Declan A. Gray ◽  
Joshua B. R. White ◽  
Abraham O. Oluwole ◽  
Parthasarathi Rath ◽  
Amy J. Glenwright ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Transport Mechanism ◽  
Protein Complexes ◽  
Native Mass Spectrometry ◽  
Structural Features ◽  
Titration Calorimetry ◽  
Binding Cavity ◽  
Shed Light

AbstractIn Bacteroidetes, one of the dominant phyla of the mammalian gut, active uptake of large nutrients across the outer membrane is mediated by SusCD protein complexes via a “pedal bin” transport mechanism. However, many features of SusCD function in glycan uptake remain unclear, including ligand binding, the role of the SusD lid and the size limit for substrate transport. Here we characterise the β2,6 fructo-oligosaccharide (FOS) importing SusCD from Bacteroides thetaiotaomicron (Bt1762-Bt1763) to shed light on SusCD function. Co-crystal structures reveal residues involved in glycan recognition and suggest that the large binding cavity can accommodate several substrate molecules, each up to ~2.5 kDa in size, a finding supported by native mass spectrometry and isothermal titration calorimetry. Mutational studies in vivo provide functional insights into the key structural features of the SusCD apparatus and cryo-EM of the intact dimeric SusCD complex reveals several distinct states of the transporter, directly visualising the dynamics of the pedal bin transport mechanism.

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