Contextual Specificity in Peptide-Mediated Protein Interactions

Most biological processes are regulated through complex networks of transient protein interactions where a globular domain in one protein recognizes a linear peptide from another, creating a relatively small contact interface. Although sufficient to ensure binding, these linear motifs alone are usually too short to achieve the high specificity observed, and additional contacts are often encoded in the residues surrounding the motif (i.e. the context). Here, we systematically identified all instances of peptide-mediated protein interactions of known three-dimensional structure and used them to investigate the individual contribution of motif and context to the global binding energy. We found that, on average, the context is responsible for roughly 20% of the binding and plays a crucial role in determining interaction specificity, by either improving the affinity with the native partner or impeding non-native interactions. We also studied and quantified the topological and energetic variability of interaction interfaces, finding a much higher heterogeneity in the context residues than in the consensus binding motifs. Our analysis partially reveals the molecular mechanisms responsible for the dynamic nature of peptide-mediated interactions, and suggests a global evolutionary mechanism to maximise the binding specificity. Finally, we investigated the viability of non-native interactions and highlight cases of potential cross-reaction that might compensate for individual protein failure and establish backup circuits to increase the robustness of cell networks

3did: interacting protein domains of known three-dimensional structure

The database of 3D Interacting Domains (3did) is a collection of domain–domain interactions in proteins for which high-resolution three-dimensional structures are known. 3did exploits structural information to provide critical molecular details necessary for understanding how interactions occur. It also offers an overview of how similar in structure are interactions between different members of the same protein family. The database also contains Gene Ontology-based functional annotations and interactions between yeast proteins from large-scale interaction discovery studies. A web-based tool to query 3did is available at http://3did.embl.de

The true price of external health effects from food consumption

Although global food consumption costs more in terms of impact on human life than money is spent on it, health costs have not been consistently quantified or included in food prices to date. In this paper, a method to determine the external health costs of nutrition and dietetics is developed by employing the cost-of-illness (COI) and true cost accounting (TCA) approaches. This is done exemplarily for the reference country Germany. The results show that 601.50 € per capita and 50.38 billion € in total external health costs are incurred annually due to nutrition. Overall, most costs are accrued through excessive meat consumption (32.56% of costs), deficient whole grain intake (15.42% of costs), and insufficient uptake of legumes (10.19% of costs). Comparing the external health costs with the external environmental costs in Germany, it can be seen that of the total annual costs of around 153.86 billion €, 67.26% originate from environmental impacts and 32.74% from impacts on human life. In order to achieve the 17 Sustainable Development Goals and to increase family as well as public health, there is a need to internalise these external costs into actual food prices

Soziale externe Kosten: Ein Framework zur Monetarisierung von Tierwohl zur Berechnung wahrer Lebensmittelpreise

Aufbauend auf Mindeststandards an Haltungsbedingungen wird eine Methodik entwickelt, wie Tierwohl monetär als Preisaufschlag auf Lebensmittelpreise dargestellt werden kann

Auf dem Weg zu wahren Preisen im Lebensmitteleinzelhandel: Die Mehrwertsteuer als Instrument zur Agrar-Transformation

Eine Reform des Mehrwertsteuersystems ist ein möglicher Weg für die Transformation der Agrarwirtschaft. Positive monetäre Anreize für nachhaltige Lebensmittel und negative Anreize für Produkte mit hohen Externalitäten können sowohl auf Verbraucher- als auch auf Erzeugerseite Impulse setzen

Veganismus für alle? Akzeptanz von veganer Ernährung in der Bevölkerung und Potentiale einer Transformation hin zur nachhaltigen Ernährung

Die geringe Akzeptanz von Veganismus in der Gesellschaft wird mithilfe eines Reviews und einer Konsumierendenbefragung ermittelt. Es werden Ernährungsmuster gebildet, Kaufmotive verglichen und Anreize für den Kauf nachhaltiger Produkte, sowie Faktoren für die Akzeptanz veganer Ernährung beleuchtet

Entwicklung eines Frameworks zur Monetarisierung externer Gesundheitskosten von Lebensmitteln

Basierend auf dem Über- und Unterkonsum von Lebensmitteln werden über einen Cost of Illness Ansatz die Kosten des Lebensmittelkonsums in Deutschland ermittelt. Über einen Risikofaktor werden verlorene krankheitsadjustierte Lebensjahre bestimmt und schließlich marginale Gesundheitskosten errechnet

Noch ein Label? - Meta-Label als Instrument zur Nachhaltigkeitskommunikation gegenüber Verbrauchern

Ein Meta-Label, das den Verbrauchern Orientierung für einen ökologisch, ökonomisch und ethisch bewussteren Konsum bietet, ist ein mögliches Instrument zur Veränderung und Anpassung der Lebensmittelindustrie an die aktuellen Herausforderungen der Umwelt

Co-Chaperones in Targeting and Delivery of Misfolded Proteins to the 26S Proteasome

Protein homeostasis (proteostasis) is essential for the cell and is maintained by a highly conserved protein quality control (PQC) system, which triages newly synthesized, mislocalized and misfolded proteins. The ubiquitin-proteasome system (UPS), molecular chaperones, and co-chaperones are vital PQC elements that work together to facilitate degradation of misfolded and toxic protein species through the 26S proteasome. However, the underlying mechanisms are complex and remain partly unclear. Here, we provide an overview of the current knowledge on the co-chaperones that directly take part in targeting and delivery of PQC substrates for degradation. While J-domain proteins (JDPs) target substrates for the heat shock protein 70 (HSP70) chaperones, nucleotide-exchange factors (NEFs) deliver HSP70-bound substrates to the proteasome. So far, three NEFs have been established in proteasomal delivery: HSP110 and the ubiquitin-like (UBL) domain proteins BAG-1 and BAG-6, the latter acting as a chaperone itself and carrying its substrates directly to the proteasome. A better understanding of the individual delivery pathways will improve our ability to regulate the triage, and thus regulate the fate of aberrant proteins involved in cell stress and disease, examples of which are given throughout the review