The dimerization or even oligomerization of G protein coupled receptors (GPCRs) causes ongoing, controversial debates about its functional role and the coupled biophysical, biochemical or biomedical ...implications. A continously growing number of studies hints to a relation between oligomerization and function of GPCRs and strengthens the assumption that receptor assembly plays a key role in the regulation of protein function. Additionally, progress in the structural analysis of GPCR-G protein and GPCR-ligand interactions allows to distinguish between actively functional and non-signaling complexes. Recent findings further suggest that the surrounding membrane, i.e., its lipid composition may modulate the preferred dimerization interface and as a result the abundance of distinct dimeric conformations. In this review, the association of GPCRs and the role of the membrane in oligomerization will be discussed. An overview of the different reported oligomeric interfaces is provided and their capability for signaling discussed. The currently available data is summarized with regard to the formation of GPCR oligomers, their structures and dependency on the membrane microenvironment as well as the coupling of oligomerization to receptor function.
Oligomer acceptors have recently emerged as promising photovoltaic materials for achieving high power conversion efficiency (PCE) and long‐term stability in organic solar cells (OSCs). However, the ...limited availability of diverse acceptors, resulting from the sole synthetic approach, has hindered their potential for future industrialization. In this study, we present a facile and effective stepwise approach that utilizes two consecutive Stille coupling reactions for the synthesis of oligomer acceptors. To demonstrate the feasibility of the novel approach, we successfully synthesize a trimer acceptor, Tri‐Y6‐OD, and further systematically investigate the impact of oligomerization on device performance and stability. The results reveal that this approach has significant advantages compared to the conventional method, including reduced formation of unwanted by‐products and lower difficulties in purification. Remarkably, the OSC based on PM6 : Tri‐Y6‐OD achieves an impressive PCE of 18.03 % and maintains 80 % of the initial PCE (T80) for 1523 h under illumination, surpassing the performance of the corresponding small molecule acceptor Y6‐OD‐based device. Furthermore, the versatility of the synthetic strategy in obtaining diverse acceptors is further demonstrated. Overall, our findings provide a facile, versatile and stepwise way for synthesizing oligomer acceptors, thereby facilitating the development of stable and efficient OSCs.
The stepwise method proposed to synthesize non‐fullerene oligomer acceptors via consecutive Stille coupling reactions offers significant advantages compared to the traditional approach, resulting in fewer unwanted by‐products and easier purification processes. By utilizing this method, the obtained Tri‐Y6‐OD‐based organic solar cells achieved a high power conversion efficiency of 18.03 %, along with excellent stability.
Plant disease resistance involves both detection of microbial molecular patterns by cell-surface pattern recognition receptors and detection of pathogen effectors by intracellular NLR immune ...receptors. NLRs are classified as sensor NLRs, involved in effector detection, or helper NLRs required for sensor NLR signaling. TIR-domain-containing sensor NLRs (TNLs) require helper NLRs NRG1 and ADR1 for resistance, and helper NLR activation of defense requires the lipase-domain proteins EDS1, SAG101, and PAD4. Previously, we found that NRG1 associates with EDS1 and SAG101 in a TNL activation-dependent manner X. Sun
,
, 3335 (2021). We report here how the helper NLR NRG1 associates with itself and with EDS1 and SAG101 during TNL-initiated immunity. Full immunity requires coactivation and mutual potentiation of cell-surface and intracellular immune receptor-initiated signaling B. P. M. Ngou, H.-K. Ahn, P. Ding, J. D. G. Jones,
, 110-115 (2021), M. Yuan
,
, 105-109 (2021). We find that while activation of TNLs is sufficient to promote NRG1-EDS1-SAG101 interaction, the formation of an oligomeric NRG1-EDS1-SAG101 resistosome requires the additional coactivation of cell-surface receptor-initiated defense. These data suggest that NRG1-EDS1-SAG101 resistosome formation in vivo is part of the mechanism that links intracellular and cell-surface receptor signaling pathways.
M17 leucyl aminopeptidases are metal-dependent exopeptidases that rely on oligomerization to diversify their functional roles. The M17 aminopeptidases from Plasmodium falciparum (PfA-M17) and ...Plasmodium vivax (Pv-M17) function as catalytically active hexamers to generate free amino acids from human hemoglobin and are drug targets for the design of novel antimalarial agents. However, the molecular basis for oligomeric assembly is not fully understood. In this study, we found that the active site metal ions essential for catalytic activity have a secondary structural role mediating the formation of active hexamers. We found that PfA-M17 and Pv-M17 exist in a metal-dependent dynamic equilibrium between active hexameric species and smaller inactive species that can be controlled by manipulating the identity and concentration of metals available. Mutation of residues involved in metal ion binding impaired catalytic activity and the formation of active hexamers. Structural resolution of Pv-M17 by cryoelectron microscopy and X-ray crystallography together with solution studies revealed that PfA-M17 and Pv-M17 bind metal ions and substrates in a conserved fashion, although Pv-M17 forms the active hexamer more readily and processes substrates faster than PfA-M17. On the basis of these studies, we propose a dynamic equilibrium between monomer ↔ dimer ↔ tetramer ↔ hexamer, which becomes directional toward the large oligomeric states with the addition of metal ions. This sophisticated metal-dependent dynamic equilibrium may apply to other M17 aminopeptidases and underpin the moonlighting capabilities of this enzyme family.
•Two PtL/PtG hybrid processes are proposed for upcycling CO2 into green fuels.•CO2 is converted through RWGS, Fe-based FTS and/or CO2 methanation.•A comparative analysis of the present & previous ...PtL/PtG processes is conducted.•The syncrude production of the present PtL/PtG process has been increased by 30.95%.•The total product revenue of the present PtL/PtG process has been increased by 12.73%.
Power-to-X (PtX) technologies, especially for the Power-to-Liquids (PtL) and Power-to-Gas (PtG) have attracted extensive attention recently, as promising pathways for carbon upcycling via converting CO2 into high-value products including liquid fuels and substitute natural gas (SNG). Herein, aiming at further improving the PtX process efficiency, we proposed two novel PtL/PtG hybrid processes, namely an indirect process (with RWGS unit) and a direct process (without RWGS unit) by integrating Fe-based Fischer-Tropsch synthesis (FTS) and olefin oligomerization technologies, which co-produce syncrude and SNG. Both process simulation and techno-economic analysis were implemented to evaluate the overall process performances, through various indicators involving technical indicators (e.g., syncrude production, energy efficiency, and net CO2 reduction), and economic indicators such as total capital investment, net CO2 reduction costs together with total product costs. Both proposed PtL/PtG processes are efficient in converting CO2 into valuable hydrocarbon fuels, and the syncrude production and total product revenues of indirect process are 2.35–14.58% and 7.55–8.51% higher than those of the direct process, respectively. Whereas, the direct process has lower net CO2 reduction cost of 206.09 $/tonne CO2. Moreover, the present PtL/PtG processes have higher syncrude production and total product revenues than those of our previous studies including a direct PtL/PtG process coupled with Fe-based FTS and two indirect PTL/PTG processes combined with RWGS and Fe/Co-based FTS reaction, with rates of 30.95 and 12.73% at most.
Recent progress in the use of iron-based complex pre-catalysts for ethylene reactivity is reviewed, illustrating the current state-of-the-art and the potential usefulness of such systems for ...delivering solely ethylene oligomerization or polymerization products. The problems associated with the industrial use of late transition metal complex pre-catalysts are generally regarded as catalyst deactivation and the formation of more products of lower molecular weight at elevated temperature. These problems have been addressed for iron-based complex pre-catalysts via the fine tuning of substituents of existing ligands and/or the design of new ligand sets. Results revealed that modified bis(imino)pyridyliron dichlorides were capable of operating at elevated temperatures, and were capable of delivering highly linear polyethylene. Other new models of iron complexes have achieved high activity for ethylene oligomerization and/or polymerization. Particularly successful has been the use of the 2-iminophenanthrolyliron pre-catalyst, which have now been utilized in a 500 tonne pilot plant.
DNA replication requires coordination between replication fork progression and deoxynucleotide triphosphate (dNTP)–generating metabolic pathways. We find that perturbation of ribonucleotide reductase ...(RNR) in humans elevates reactive oxygen species (ROS) that are detected by peroxiredoxin 2 (PRDX2). In the oligomeric state, PRDX2 forms a replisome-associated ROS sensor, which binds the fork accelerator TIMELESS when exposed to low levels of ROS. Elevated ROS levels generated by RNR attenuation disrupt oligomerized PRDX2 to smaller subunits, whose dissociation from chromatin enforces the displacement of TIMELESS from the replisome. This process instantly slows replication fork progression, which mitigates pathological consequences of replication stress. Thus, redox signaling couples fluctuations of dNTP biogenesis with replisome activity to reduce stress during genome duplication. We propose that cancer cells exploit this pathway to increase their adaptability to adverse metabolic conditions.
Cyclodextrins have previously been proven to be active in the catalysis of cyclic ester ring-opening reactions, hypothetically in a similar way to lipase-catalyzed reactions. However, the way they ...act remains unclear. Here, we focus on β-cyclodextrin's involvement in the synthesis and characterization of β-cyclodextrin-oligocaprolactone (CDCL) products obtained via the organo-catalyzed ring-opening of ε-caprolactone. Previously, bulk or supercritical carbon dioxide polymerizations has led to inhomogeneous products. Our approach consists of solution polymerization (dimethyl sulfoxide and dimethylformamide) to obtain homogeneous CDCL derivatives with four monomer units on average. Oligomerization kinetics, performed by a matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) optimized method in tandem with
H NMR, revealed that monomer conversion occurs in two stages: first, the monomer is rapidly attached to the secondary OH groups of β-cyclodextrin and, secondly, the monomer conversion is slower with attachment to the primary OH groups. MALDI MS was further employed for the measurement of the ring-opening kinetics to establish the influence of the solvents as well as the effect of organocatalysts (4-dimethylaminopyridine and (-)-sparteine). Additionally, the mass spectrometry structural evaluation was further enhanced by fragmentation studies which confirmed the attachment of oligoesters to the cyclodextrin and the cleavage of dimethylformamide amide bonds during the ring-opening process.
A new family of highly active ethylene tri-/tetramerization catalysts based on N-phosphinoamidinechromium complexes has been investigated. The 1-hexene to 1-octene molar ratio can be tuned from 140 ...to 1.5 by varying the steric environment around the chromium center, and product purities are very good to excellent. Precatalyst tridentate coordination effectively shuts down catalytic activity, suggesting that THF abstraction from the chromium center by the Lewis acidic aluminum activator is necessary to achieve an active catalyst system.
Proanthocyanidins (PAs) are natural polymers of flavan-3-ols, commonly (+)-catechin and (-)-epicatechin. However, exactly how PA oligomerization proceeds is poorly understood. Here we show, both ...biochemically and genetically, that ascorbate (AsA) is an alternative "starter unit" to flavan-3-ol monomers for leucocyanidin-derived (+)-catechin subunit extension in the Arabidopsis thaliana anthocyanidin synthase (ans) mutant. These (catechin)
:ascorbate conjugates (AsA-C
) also accumulate throughout the phase of active PA biosynthesis in wild-type grape flowers, berry skins and seeds. In the presence of (-)-epicatechin, AsA-C
can further provide monomeric or oligomeric PA extension units for non-enzymatic polymerization in vitro, and their role in vivo is inferred from analysis of relative metabolite levels in both Arabidopsis and grape. Our findings advance the knowledge of (+)-catechin-type PA extension and indicate that PA oligomerization does not necessarily proceed by sequential addition of a single extension unit. AsA-C
defines a new type of PA intermediate which we term "sub-PAs".
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