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The slope of the quasi-linear relation between planetary outgoing longwave radiation (OLR) and surface temperature (T_S) is an important parameter measuring the sensitivity of Earth’s climate system. The primary objective of this study is to seek a general explanation for the quasi-linear OLR–T_Srelation that remains valid regardless of the strength of the atmospheric window’s narrowing effect on planetary thermal emission at higher temperatures. The physical understanding of the quasi-linear OLR–T_Srelation and its slope is gained from observation analysis, climate simulations with radiative–convective equilibrium and general circulation models, and a series of online feedback suppression experiments. The observed quasi-linear OLR–T_Srelation manifests a climate footprint of radiative (such as the greenhouse effect) and nonradiative processes (poleward energy transport). The former acts to increase the meridional gradient of surface temperature and the latter decreases the meridional gradient of atmospheric temperatures, causing the flattening of the meridional profile of the OLR. Radiative processes alone can lead to a quasi-linear OLR–T_Srelation that is more steeply sloped. The atmospheric poleward energy transport alone can also lead to a quasi-linear OLR–T_Srelation by rerouting part of the OLR to be emitted from a warmer place to a colder place. The combined effects of radiative and nonradiative processes make the quasi-linear OLR–T_Srelation less sloped with a higher degree of linearity. In response to anthropogenic radiative forcing, the slope of the quasi-linear OLR–T_Srelation is further reduced via stronger water vapor feedback and enhanced poleward energy transport.

The slope of the quasi-linear relation between planetary outgoing longwave radiation (OLR) and surface temperature (T_S) is an important parameter measuring the sensitivity of Earth’s climate system. The observed quasi-linear OLR–T_Srelation manifests a climate footprint of radiative (greenhouse effect) and nonradiative processes (poleward energy transport). Radiative processes alone can lead to a quasi-linear OLR–T_Srelation that is more steeply sloped. The atmospheric poleward energy transport alone can also lead to a quasi-linear OLR–T_Srelation by rerouting part of the OLR to be emitted from a warmer place to a colder place. The combined effects of radiative and nonradiative processes make the quasi-linear OLR–T_Srelation less sloped with a higher degree of linearity.

 

The scaffold protein PSD-95 links postsynaptic receptors to sites of presynaptic neurotransmitter release. Flexible linkers between folded domains in PSD-95 enable a dynamic supertertiary structure. Interdomain interactions within the PSG supramodule, formed by P DZ3, S H3, and G uanylate Kinase domains, regulate PSD-95 activity. Here we combined discrete molecular dynamics and single molecule Förster resonance energy transfer (FRET) to characterize the PSG supramodule, with time resolution spanning picoseconds to seconds. We used a FRET network to measure distances in full-length PSD-95 and model the conformational ensemble. We found that PDZ3 samples two conformational basins, which we confirmed with disulfide mapping. To understand effects on activity, we measured binding of the synaptic adhesion protein neuroligin. We found that PSD-95 bound neuroligin well at physiological pH while truncated PDZ3 bound poorly. Our hybrid structural models reveal how the supertertiary context of PDZ3 enables recognition of this critical synaptic ligand. 

Thiamine pyrophosphate (TPP) riboswitches regulate thiamine metabolism by inhibiting the translation of enzymes essential to thiamine synthesis pathways upon binding to thiamine pyrophosphate in cells across all domains of life. Recent work on the Arabidopsis thaliana TPP riboswitch suggests a multistep TPP binding process involving multiple riboswitch configurational ensembles and Mg 2+ dependence underlies the mechanism of TPP recognition and subsequent transition to the expression-inhibiting state of the aptamer domain followed by changes in the expression platform. However, details of the relationship between TPP riboswitch conformational changes and interactions with TPP and Mg 2+ in the aptamer domain constituting this mechanism are unknown. Therefore, we integrated single-molecule multiparameter fluorescence and force spectroscopy with atomistic molecular dynamics simulations and found that conformational transitions within the aptamer domain's sensor helices associated with TPP and Mg 2+ ligand binding occurred between at least five different ensembles on timescales ranging from µs to ms. These dynamics are orders of magnitude faster than the 10 sec-timescale folding kinetics associated with expression-state switching in the switch helix. Together, our results show that a TPP and Mg 2+ dependent mechanism determines dynamic configurational state ensemble switching of the aptamer domain's sensor helices that regulate the switch helix's stability, which ultimately may lead to the expression-inhibiting state of the riboswitch. Additionally, we propose that two pathways exist for ligand recognition and that this mechanism underlies a kinetic rheostat-like behavior of the Arabidopsis thaliana TPP riboswitch. 

Suckerin in squid sucker ring teeth is a block‐copolymer peptide comprised of two repeating modules—the alanine and histidine‐rich M1 and the glycine‐rich M2. Suckerin self‐assemblies display excellent thermo‐plasticity and pH‐responsive properties, along with the high biocompatibility, biodegradability, and sustainability. However, the self‐assembly mechanism and the detailed role of each module are still elusive, limiting the capability of applying and manipulating such biomaterials. Here, the self‐assembly dynamics of the two modules and two minimalist suckerin‐mimetic block‐copolymers, M1‐M2‐M1 and M2‐M1‐M2, in silico is investigated. The simulation results demonstrate that M2 has a stronger self‐association but weaker β‐sheet propensities than M1. The high self‐assembly propensity of M2 allows the minimalist block‐copolymer peptides to coalesce with microphase separation, enabling the formation of nanoconfined β‐sheets in the matrix formed by M1–M2 contacts. Since these glycine‐rich fragments with scatted hydrophobic and aromatic residues are building blocks of many other block‐copolymer peptides, the study suggests that these modules function as the “molecular glue” in addition to the flexible linker or spacer to drive the self‐assembly and microphase separation. The uncovered molecular insights may help understand the structure and function of suckerin and also aid in the design of functional block‐copolymer peptides for nanotechnology and biomedicine applications.

 

Oligomers populated during the early amyloid aggregation process are more toxic than mature fibrils, but pinpointing the exact toxic species among highly dynamic and heterogeneous aggregation intermediates remains a major challenge. β-barrel oligomers, structurally-determined recently for a slow-aggregating peptide derived from αB crystallin, are attractive candidates for exerting amyloid toxicity due to their well-defined structures as therapeutic targets and compatibility to the “amyloid-pore” hypothesis of toxicity. To assess whether β-barrel oligomers are common intermediates to amyloid peptides - a necessary step toward associating β-barrel oligomers with general amyloid cytotoxicity, we computationally studied the oligomerization and fibrillization dynamics of seven well-studied fragments of amyloidogenic proteins with different experimentally-determined aggregation morphologies and cytotoxicity. In our molecular dynamics simulations, β-barrel oligomers were only observed in five peptides self-assembling into the characteristic cross-β aggregates, but not the other two that formed polymorphic β-rich aggregates as reported experimentally. Interestingly, the latter two peptides were previously found nontoxic. Hence, the observed correlation between β-barrel oligomers formation and cytotoxicity supports the hypothesis of β-barrel oligomers as the common toxic intermediates of amyloid aggregation.