Temperature-induced cell death is thought to be due to protein denaturation, but the determinants of thermal sensitivity of proteomes remain largely uncharacterized. We developed a structural ...proteomic strategy to measure protein thermostability on a proteome-wide scale and with domain-level resolution. We applied it to
,
,
, and human cells, yielding thermostability data for more than 8000 proteins. Our results (i) indicate that temperature-induced cellular collapse is due to the loss of a subset of proteins with key functions, (ii) shed light on the evolutionary conservation of protein and domain stability, and (iii) suggest that natively disordered proteins in a cell are less prevalent than predicted and (iv) that highly expressed proteins are stable because they are designed to tolerate translational errors that would lead to the accumulation of toxic misfolded species.
Elucidating complex phosphorylation events in signaling pathways on a proteome-wide scale is a major endeavor. In this issue, Humphrey et al.1 present EasyPhos, a simplified pipeline for large-scale ...protein phosphorylation analysis that maximizes throughput and phospho proteome coverage while minimizing technical variability.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
To a large extent functional diversity in cells is achieved by the expansion of molecular complexity beyond that of the coding genome. Various processes create multiple distinct but related proteins ...per coding gene - so-called proteoforms - that expand the functional capacity of a cell. Evaluating proteoforms from classical bottom-up proteomics datasets, where peptides instead of intact proteoforms are measured, has remained difficult. Here we present COPF, a tool for COrrelation-based functional ProteoForm assessment in bottom-up proteomics data. It leverages the concept of peptide correlation analysis to systematically assign peptides to co-varying proteoform groups. We show applications of COPF to protein complex co-fractionation data as well as to more typical protein abundance vs. sample data matrices, demonstrating the systematic detection of assembly- and tissue-specific proteoform groups, respectively, in either dataset. We envision that the presented approach lays the foundation for a systematic assessment of proteoforms and their functional implications directly from bottom-up proteomic datasets.
Cells respond to stress by blocking translation, rewiring metabolism and forming transient messenger ribonucleoprotein assemblies called stress granules (SGs). After stress release, re-establishing ...homeostasis and disassembling SGs requires ATP-consuming processes. However, the molecular mechanisms whereby cells restore ATP production and disassemble SGs after stress remain poorly understood. Here we show that upon stress, the ATP-producing enzyme Cdc19 forms inactive amyloids, and that their rapid re-solubilization is essential to restore ATP production and disassemble SGs in glucose-containing media. Cdc19 re-solubilization is initiated by the glycolytic metabolite fructose-1,6-bisphosphate, which directly binds Cdc19 amyloids, allowing Hsp104 and Ssa2 chaperone recruitment and aggregate re-solubilization. Fructose-1,6-bisphosphate then promotes Cdc19 tetramerization, which boosts its activity to further enhance ATP production and SG disassembly. Together, these results describe a molecular mechanism that is critical for stress recovery and directly couples cellular metabolism with SG dynamics via the regulation of reversible Cdc19 amyloids.
This literature review deals with the well-known problem of soiling in solar plants, which it severely affects the energy yield of solar power plants. A loss of reflectivity due to soiling reduces ...the entire productivity of the plant by limiting the energy harvested (i.e. the incoming direct normal irradiance is not properly reflected towards the right focus). On the other hand, the costs of maintenance and cleaning of the collectors represent a significant component of the plant operational costs. Therefore, in this paper, a multi-disciplinary literature review is conducted with the aim of collecting existing models for the key processes, organising them into a ‘dust life cycle’. This cycle is divided into four steps: Generation, Deposition, Adhesion, and Removal; with emphasis on the interaction between dust particles and solar collectors’ surfaces. Generation deals with the loading of atmosphere with dust particles, deposition concerns the processes that actually bring airborne dust onto the collectors’ surface, adhesion and removal represent the competing forces whose balance determine which particles remains adherent on the collectors and which are detached. The intent is to provide a complete framework for the development of a future physical model for the prediction and estimation of the actual soiling of the solar collectors, which engineers can implement in order to maximize the revenues of CSP plant, pushing towards more clean and sustainable energy production technologies.
Metabolite-protein interactions control a variety of cellular processes, thereby playing a major role in maintaining cellular homeostasis. Metabolites comprise the largest fraction of molecules in ...cells, but our knowledge of the metabolite-protein interactome lags behind our understanding of protein-protein or protein-DNA interactomes. Here, we present a chemoproteomic workflow for the systematic identification of metabolite-protein interactions directly in their native environment. The approach identified a network of known and novel interactions and binding sites in Escherichia coli, and we demonstrated the functional relevance of a number of newly identified interactions. Our data enabled identification of new enzyme-substrate relationships and cases of metabolite-induced remodeling of protein complexes. Our metabolite-protein interactome consists of 1,678 interactions and 7,345 putative binding sites. Our data reveal functional and structural principles of chemical communication, shed light on the prevalence and mechanisms of enzyme promiscuity, and enable extraction of quantitative parameters of metabolite binding on a proteome-wide scale.
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•Chemical proteomics provides a map of metabolite-protein interactions•Metabolite binding sites pinpointed on a proteome-wide scale•New catalytic, allosteric, and metabolite-induced protein-protein interaction events•Binding of metabolites at binding sites is promiscuous
A method to assess proteome-wide binding to metabolites of interest uncovers new allosteric and enzymatic functions and provides a tool to investigate drug targets in the native cellular environment.
By delivering precise, reproducible quantification of proteins of interest in biological samples, targeted proteomics approaches are allowing researchers to apply the scientific method using mass ...spectrometry. A look at how researchers are using proteomics to expand their scientific knowledge is offered.
Climate variations in both space and time can impact mountain topography and drainage-basin morphology through a variety of surface processes. This is illustrated dramatically in the Ordos Block of ...northern China, which encompasses the main body of the Loess Plateau in the southeast and the Mu Us Desert in the northwest. The plateau is known for severe soil erosion by fluvial processes; whereas the desert is dominated by aeolian processes. Here we characterize the spatial transition in landscape relief and drainage network integration of the middle Ordos Block, corresponding to a precipitation gradient across the region, that is otherwise homogeneous in terms of its tectonics and bedrock. Differences in landscape relief and drainage network integration occur over a short range in precipitation rate, and outside this transition zone, landscape morphologic metrics appear to be relatively insensitive to precipitation. Where precipitation rates are greater than ∼420 mm/yr, landscapes are characterized by integrated drainage networks with relief over 100 m within a 1 km radius. With precipitation rates lower than ∼380 mm/yr, the landscapes tend to have lower relief, discontinuous channels and hundreds of playa lakes indicating inefficient runoff. Combined with stratigraphic records, we posit that continuous drainage networks in the semi-arid to arid transition zone expand in wetter periods, and shrink and fragment when precipitation falls below a threshold. Today the Ordos Block is experiencing the transition from a drier (glacial) stage to a wetter (interglacial) stage, with higher precipitation rates over the past ∼12 thousand years. It follows that fluvial processes likely have increased in efficiency and are currently advancing into regions to the northwest formerly dominated by aeolian processes. Our findings suggest that a component of the severe sediment erosion of the Loess Plateau is a transient feature locally associated with glacial-interglacial climate change and the transition from aeolian- to fluvial-dominated surface processes.
•Relief and drainage network change over a short range in precipitation rate.•The drainage network variations shift laterally over glacial-interglacial cycles.•A component of the high sediment supply to the Yellow River is a transient feature.
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