scholarly journals Phase Separation of Shell Protein and Enzyme: An Insight into the Biogenesis of a Prokaryotic Metabolosome

2022 ◽  
Author(s):  
Gaurav Kumar ◽  
Sharmistha Sinha
Keyword(s):  
Phase Separation ◽  
Protein Interactions ◽  
Self Assembly ◽  
Bacterial Species ◽  
Protein Structures ◽  
The Self ◽  
Liquid Droplets ◽  
Shell Protein ◽  
Shell Proteins

Bacterial microcompartments are substrate specific metabolic modules that are conditionally expressed in certain bacterial species. These all protein structures have size in the range of 100-150 nm and are formed by the self-assembly of thousands of protein subunits, all encoded by genes belonging to a single operon. The operon contains genes that encode for both enzymes and shell proteins. The shell proteins self-assemble to form the outer coat of the compartment and enzymes are encapsulated within. A perplexing question in MCP biology is to understand the mechanism which governs the formation of these small yet complex assemblages of proteins. In this work we use 1,2-propanediol utilization microcompartments (PduMCP) as a paradigm to identify the factors that drive the self-assembly of MCP proteins. We find that a major shell protein PduBB tend to self-assemble under macromolecular crowded environment and suitable ionic strength. Microscopic visualization and biophysical studies reveal phase separation to be the principle mechanism behind the self-association of shell protein in the presence of salts and macromolecular crowding. The shell protein PduBB interacts with the enzyme diol-dehydratase PduCDE and co-assemble into phase separated liquid droplets. The co-assembly of PduCDE and PduBB results in the enhancement of catalytic activity of the enzyme. A combination of spectroscopic and biochemical techniques shows the relevance of divalent cation Mg2+ in providing stability to intact PduMCP in vivo. Together our results suggest a combination of protein-protein interactions and phase separation guiding the self-assembly of Pdu shell protein and enzyme in solution phase.

The Origin of the Eukaryotic Cell Based on Conservation of Existing Interfaces

2006 ◽  
Vol 12 (4) ◽  
pp. 513-523 ◽  
Author(s):  
Albert D. G. de Roos
Keyword(s):  
Plasma Membrane ◽  
Protein Interactions ◽  
Self Assembly ◽  
Evolutionary Model ◽  
Lipid Vesicles ◽  
Eukaryotic Cell ◽  
The Self ◽  
Lipid Protein Interactions

Current theories about the origin of the eukaryotic cell all assume that during evolution a prokaryotic cell acquired a nucleus. Here, it is shown that a scenario in which the nucleus acquired a plasma membrane is inherently less complex because existing interfaces remain intact during evolution. Using this scenario, the evolution to the first eukaryotic cell can be modeled in three steps, based on the self-assembly of cellular membranes by lipid-protein interactions. First, the inclusion of chromosomes in a nuclear membrane is mediated by interactions between laminar proteins and lipid vesicles. Second, the formation of a primitive endoplasmic reticulum, or exomembrane, is induced by the expression of intrinsic membrane proteins. Third, a plasma membrane is formed by fusion of exomembrane vesicles on the cytoskeletal protein scaffold. All three self-assembly processes occur both in vivo and in vitro. This new model provides a gradual Darwinistic evolutionary model of the origins of the eukaryotic cell and suggests an inherent ability of an ancestral, primitive genome to induce its own inclusion in a membrane.

Kinetic theory of protein filament growth: Self-consistent methods and perturbative techniques

2014 ◽  
Vol 29 (02) ◽  
pp. 1530002 ◽  
Author(s):  
Thomas C. T. Michaels ◽  
Tuomas P. J. Knowles
Keyword(s):  
Self Assembly ◽  
Protein Structures ◽  
Filamentous Growth ◽  
Molecular Structures ◽  
The Self ◽  
Rate Equations ◽  
Disease States ◽  
Self Consistent ◽  
Monomeric Proteins ◽  
General Physical

Filamentous protein structures are of high relevance for the normal functioning of the cell, where they provide the structural component for the cytoskeleton, but are also implicated in the pathogenesis of many disease states. The self-assembly of these supra-molecular structures from monomeric proteins has been studied extensively in the past 50 years and much interest has focused on elucidating the microscopic events that drive linear growth phenomena in a biological setting. Master equations have proven to be particularly fruitful in this context, allowing specific assembly mechanisms to be linked directly to experimental observations of filamentous growth. Recently, these approaches have increasingly been applied to aberrant protein polymerization, elucidating potential implications for controlling or combating the formation of pathological filamentous structures. This article reviews recent theoretical advances in the field of filamentous growth phenomena through the use of the master-equation formalism. We use perturbation and self-consistent methods for obtaining analytical solutions to the rate equations describing fibrillar growth and show how the resulting closed-form expressions can be used to shed light on the general physical laws underlying this complex phenomenon. We also present a connection between the underlying ideas of the self-consistent analysis of filamentous growth and the perturbative renormalization group.

scholarly journals Pharmacophore hybridisation and nanoscale assembly to discover self-delivering lysosomotropic new-chemical entities for cancer therapy

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhao Ma ◽  
Jin Li ◽  
Kai Lin ◽  
Mythili Ramachandran ◽  
Dalin Zhang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Therapy ◽  
Self Assembly ◽  
The Self ◽  
Single Drug ◽  
Drug Nanoparticles ◽  
Lysosomal Dysfunction ◽  
New Chemical Entities ◽  
Autophagy Inhibition

Abstract Integration of the unique advantages of the fields of drug discovery and drug delivery is invaluable for the advancement of drug development. Here we propose a self-delivering one-component new-chemical-entity nanomedicine (ONN) strategy to improve cancer therapy through incorporation of the self-assembly principle into drug design. A lysosomotropic detergent (MSDH) and an autophagy inhibitor (Lys05) are hybridised to develop bisaminoquinoline derivatives that can intrinsically form nanoassemblies. The selected BAQ12 and BAQ13 ONNs are highly effective in inducing lysosomal disruption, lysosomal dysfunction and autophagy blockade and exhibit 30-fold higher antiproliferative activity than hydroxychloroquine used in clinical trials. These single-drug nanoparticles demonstrate excellent pharmacokinetic and toxicological profiles and dramatic antitumour efficacy in vivo. In addition, they are able to encapsulate and deliver additional drugs to tumour sites and are thus promising agents for autophagy inhibition-based combination therapy. Given their transdisciplinary advantages, these BAQ ONNs have enormous potential to improve cancer therapy.

scholarly journals The self assembly of proteins; probing patchy protein interactions

2015 ◽  
Vol 17 (7) ◽  
pp. 5413-5420 ◽  
Author(s):  
Susan James ◽  
Michelle K. Quinn ◽  
Jennifer J. McManus
Keyword(s):  
Phase Diagram ◽  
Thermodynamic Properties ◽  
Protein Interactions ◽  
Self Assembly ◽  
The Self ◽  
Protein Surface ◽  
Competing Interactions ◽  
Diagram Approach

Anisotropy is central to protein self-assembly. The kinetic and thermodynamic properties of proteins in which competing interactions exist due to the anisotropic or patchy nature of the protein surface have been explored using a phase diagram approach.

Nanomanufacturing of high-performance hollow fiber nanofiltration membranes by coating uniform block polymer films from solution

2017 ◽  
Vol 5 (7) ◽  
pp. 3358-3370 ◽  
Author(s):  
Yizhou Zhang ◽  
Ryan A. Mulvenna ◽  
Bryan W. Boudouris ◽  
William A. Phillip
Keyword(s):  
Phase Separation ◽  
Hollow Fiber ◽  
Self Assembly ◽  
High Performance ◽  
Polymer Membranes ◽  
Dip Coating ◽  
The Self ◽  
Separation Method ◽  
Nanofiltration Membranes ◽  
Block Polymer

Block polymer membranes in the hollow fiber geometry were fabricated by combining the dip-coating archetype with the self-assembly and non-solvent induced phase separation method.

Phase separation and selective guest–host binding in multi-component supramolecular self-assembly on Au(111)

2018 ◽  
Vol 54 (75) ◽  
pp. 10570-10573 ◽  
Author(s):  
Linghao Yan ◽  
Guowen Kuang ◽  
Nian Lin
Keyword(s):  
Phase Separation ◽  
Self Assembly ◽  
The Self ◽  
Trimesic Acid

We find a phase separation and selective guest–host inclusion in the self-assembly of trimesic acid, benzenetribenzoic acid and coronene on Au(111).

scholarly journals Phase separation of both a plant virus movement protein and cellular factors support virus-host interactions

2021 ◽  
Author(s):  
Shelby L Brown ◽  
Jared P. May
Keyword(s):  
Phase Separation ◽  
Mosaic Virus ◽  
Self Assembly ◽  
Electrostatic Interactions ◽  
Movement Protein ◽  
Virus Movement ◽  
In Planta ◽  
Ribonucleoprotein Complexes

Phase separation concentrates biomolecules, which should benefit RNA viruses that must sequester viral and host factors during an infection. Here, the p26 movement protein from Pea enation mosaic virus 2 (PEMV2) was found to phase separate and partition in nucleoli and G3BP stress granules (SGs) in vivo . Electrostatic interactions drive p26 phase separation as mutation of basic (R/K-G) or acidic (D/E-G) residues either blocked or reduced phase separation, respectively. During infection, p26 must partition inside the nucleolus and interact with fibrillarin (Fib2) as a pre-requisite for systemic trafficking of viral RNAs. Partitioning of p26 in pre-formed Fib2 droplets was dependent on p26 phase separation suggesting that phase separation of viral movement proteins supports nucleolar partitioning and virus movement. Furthermore, viral ribonucleoprotein complexes containing p26, Fib2, and PEMV2 RNA were formed via phase separation in vitro and could provide the basis for self-assembly in planta . Interestingly, both R/K-G and D/E-G p26 mutants failed to support systemic trafficking of a Tobacco mosaic virus (TMV) vector in Nicotiana benthamiana suggesting that p26 phase separation, proper nucleolar partitioning, and systemic movement are intertwined. p26 also partitioned in SGs and G3BP over-expression restricted PEMV2 accumulation >20-fold. Expression of phase separation-deficient G3BP only restricted PEMV2 5-fold, demonstrating that G3BP phase separation is critical for maximum antiviral activity.

scholarly journals Construction and Characterizations of Antibacterial Surfaces Based on Self-Assembled Monolayer of Antimicrobial Peptides (Pac-525) Derivatives on Gold

Coatings ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1014
Author(s):  
Zijiao Zhang ◽  
Ni Kou ◽  
Weilong Ye ◽  
Shuo Wang ◽  
Jiaju Lu ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Self Assembly ◽  
The Self ◽  
Self Assembled Monolayer ◽  
E Coli ◽  
Antimicrobial Efficiency ◽  
Gold Substrates ◽  
Self Assembled ◽  
Antibacterial Surfaces

Background: Infection that is related to implanted biomaterials is a serious issue in the clinic. Antimicrobial peptides (AMPs) have been considered as an ideal alternative to traditional antibiotic drugs, for the treatment of infections, while some problems, such as aggregation and protein hydrolysis, are still the dominant concerns that compromise their antimicrobial efficiency in vivo. Methods: In this study, antimicrobial peptides underwent self-assembly on gold substrates, forming good antibacterial surfaces, with stable antibacterial behavior. The antimicrobial ability of AMPs grafted on the surfaces, with or without glycine spaces or a primer layer, was evaluated. Results: Specifically, three Pac-525 derivatives, namely, Ac-CGn-KWRRWVRWI-NH2 (n = 0, 2, or 6) were covalently grafted onto gold substrates via the self-assembling process for inhibiting the growth of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Furthermore, the alkanethiols HS(CH)10SH were firstly self-assembled into monolayers, as a primer layer (SAM-SH) for the secondary self-assembly of Pac-525 derivatives, to effectively enhance the bactericidal performance of the grafted AMPs. The -(CH)10-S-S-G6Pac derivative was highly effective against S. aureus and E. coli, and reduced the viable amount of E. coli and S. aureus to 0.4% and 33.2%, respectively, after 24 h of contact. In addition, the immobilized AMPs showed good biocompatibility, promoting bone marrow stem cell proliferation. Conclusion: the self-assembled monolayers of the Pac-525 derivatives have great potential as a novel therapeutic method for the treatment of implanted biomaterial infections.

scholarly journals Pat1 promotes processing body assembly by enhancing the phase separation of the DEAD-box ATPase Dhh1 and RNA

2018 ◽  
Author(s):  
Ruchika Sachdev ◽  
Maria Hondele ◽  
Miriam Linsenmeier ◽  
Pascal Vallotton ◽  
Christopher F. Mugler ◽  
...  
Keyword(s):  
Phase Separation ◽  
Direct Interaction ◽  
Liquid Droplets ◽  
Processing Bodies ◽  
Dead Box ◽  
The Dead ◽  
Processing Body ◽  
Liquid Liquid Phase Separation

AbstractProcessing bodies (PBs) are cytoplasmic mRNP granules that assemble via liquid-liquid phase separation and are implicated in the decay or storage of mRNAs. How PB assembly is regulated in cells remains unclear. We recently identified the ATPase activity of the DEAD-box protein Dhh1 as a key regulator of PB dynamics and demonstrated that Not1, an activator of the Dhh1 ATPase and member of the CCR4-NOT deadenylase complex inhibits PB assembly in vivo [Mugler et al., 2016]. Here, we show that the PB component Pat1 antagonizes Not1 and promotes PB assembly via its direct interaction with Dhh1. Intriguingly, in vivo PB dynamics can be recapitulated in vitro, since Pat1 enhances the phase separation of Dhh1 and RNA into liquid droplets, whereas Not1 reverses Pat1-Dhh1-RNA condensation. Overall, our results uncover a function of Pat1 in promoting the multimerization of Dhh1 on mRNA, thereby aiding the assembly of large multivalent mRNP granules that are PBs.

Sign in / Sign up

Export Citation Format

Share Document