From the first to the second domain of gelsolin: a common path on the surface of actin?11Data deposition: The atomic coordinates and merged structure factors have been deposited in the Protein Data Bank, www.rcsb.org (PDB ID code 1P8Z).

AbstractWe present the 2.6 Å resolution crystal structure of a complex formed between G-actin and gelsolin fragment Met25–Gln160 (G1+). The structure differs from those of other gelsolin domain 1 (G1) complexes in that an additional six amino acid residues from the crucial linker region into gelsolin domain 2 (G2) are visible and are attached securely to the surface of actin. The linker segment extends away from G1 up the face of actin in a direction that infers G2 will bind along the same long-pitch helical strand as the actin bound to G1. This is consistent with a mechanism whereby G2 attaches gelsolin to the side of a filament and then directs G1 toward a position where it would disrupt actin–actin contacts. Alignment of the sequence of the structurally important residues within the G1–G2 linker with those of WH2 (WASp homology domain 2) domain protein family members (e.g. WASp (Wiscott–Aldridge syndrome protein) and thymosin β4) suggests that the opposing activities of filament assembly and disassembly may exploit a common patch on the surface of actin

The role of hydration in protein stability: comparison of the cold and heat unfolded States of yfh1

Protein unfolding occurs at both low and high temperatures, although in most cases, only the high-temperature transition can be experimentally studied. A pressing question is how much the low- and high-temperature denatured states, although thermodynamically equivalent, are structurally and kinetically similar. We have combined experimental and computational approaches to compare the high- and low-temperature unfolded states of Yfh1, a natural protein that, at physiologic pH, undergoes cold and heat denaturation around 0 °C and 40 °C without the help of ad hoc destabilization. We observe that the two denatured states have similar but not identical residual secondary structures, different kinetics and compactness and a remarkably different degree of hydration. We use molecular dynamics simulations to rationalize the role of solvation and its effect on protein stability

Ca2+ binding by domain 2 plays a critical role in the activation and stabilization of gelsolin

Gelsolin consists of six homologous domains (G1–G6), each containing a conserved Ca-binding site. Occupation of a subset of these sites enables gelsolin to sever and cap actin filaments in a Ca-dependent manner. Here, we present the structures of Ca-free human gelsolin and of Ca-bound human G1–G3 in a complex with actin. These structures closely resemble those determined previously for equine gelsolin. However, the G2 Ca-binding site is occupied in the human G1–G3/actin structure, whereas it is vacant in the equine version. In-depth comparison of the Ca-free and Ca-activated, actin-bound human gelsolin structures suggests G2 and G6 to be cooperative in binding Ca2+ and responsible for opening the G2–G6 latch to expose the F-actin-binding site on G2. Mutational analysis of the G2 and G6 Ca-binding sites demonstrates their interdependence in maintaining the compact structure in the absence of calcium. Examination of Ca binding by G2 in human G1–G3/actin reveals that the Ca2+ locks the G2–G3 interface. Thermal denaturation studies of G2–G3 indicate that Ca binding stabilizes this fragment, driving it into the active conformation. The G2 Ca-binding site is mutated in gelsolin from familial amyloidosis (Finnish-type) patients. This disease initially proceeds through protease cleavage of G2, ultimately to produce a fragment that forms amyloid fibrils. The data presented here support a mechanism whereby the loss of Ca binding by G2 prolongs the lifetime of partially activated, intermediate conformations in which the protease cleavage site is exposed

Lessons from the 2018-2019 European droughts: a collective need for unifying drought risk management

Drought events and their impacts vary spatially and temporally due to diverse pedo-climatic and hydrologic conditions, as well as variations in exposure and vulnerability, such as demographics and response actions. While hazard severity and frequency of past drought events have been studied in detail, little is known about the effect of drought management strategies on the actual impacts and how the hazard is perceived by relevant stakeholders. In a continental study, we characterised and assessed the impacts and the perceptions of two recent drought events (2018 and 2019) in Europe and examined the relationship between management strategies and drought perception, hazard, and impact. The study was based on a pan-European survey involving national representatives from 28 countries and relevant stakeholders responding to a standard questionnaire. The survey focused on collecting information on stakeholders' perceptions of drought, impacts on water resources and beyond, water availability, and current drought management strategies on national and regional scales. The survey results were compared with the actual drought hazard information registered by the European Drought Observatory (EDO) for 2018 and 2019. The results highlighted high diversity in drought perception across different countries and in values of the implemented drought management strategies to alleviate impacts by increasing national and sub-national awareness and resilience. The study identifies an urgent need to further reduce drought impacts by constructing and implementing a European macro-level drought governance approach, such as a directive, which would strengthen national drought management and mitigate damage to human and natural assets

Lessons from the 2018-2019 European droughts: a collective need for unifying drought risk management

Drought events and their impacts vary spatially and temporally due to diverse pedo-climatic and hydrologic conditions, as well as variations in exposure and vulnerability, such as demographics and response actions. While hazard severity and frequency of past drought events have been studied in detail, little is known about the effect of drought management strategies on the actual impacts and how the hazard is perceived by relevant stakeholders. In a continental study, we characterised and assessed the impacts and the perceptions of two recent drought events (2018 and 2019) in Europe and examined the relationship between management strategies and drought perception, hazard, and impact. The study was based on a pan-European survey involving national representatives from 28 countries and relevant stakeholders responding to a standard questionnaire. The survey focused on collecting information on stakeholders' perceptions of drought, impacts on water resources and beyond, water availability, and current drought management strategies on national and regional scales. The survey results were compared with the actual drought hazard information registered by the European Drought Observatory (EDO) for 2018 and 2019. The results highlighted high diversity in drought perception across different countries and in values of the implemented drought management strategies to alleviate impacts by increasing national and sub-national awareness and resilience. The study identifies an urgent need to further reduce drought impacts by constructing and implementing a European macro-level drought governance approach, such as a directive, which would strengthen national drought management and mitigate damage to human and natural assets