Role of Hsp70 ATPase Domain Intrinsic Dynamics and Sequence Evolution in Enabling its Functional Interactions with NEFs

Catalysis of ADP-ATP exchange by nucleotide exchange factors (NEFs) is central to the activity of Hsp70 molecular chaperones. Yet, the mechanism of interaction of this family of chaperones with NEFs is not well understood in the context of the sequence evolution and structural dynamics of Hsp70 ATPase domains. We studied the interactions of Hsp70 ATPase domains with four different NEFs on the basis of the evolutionary trace and co-evolution of the ATPase domain sequence, combined with elastic network modeling of the collective dynamics of the complexes. Our study reveals a subtle balance between the intrinsic (to the ATPase domain) and specific (to interactions with NEFs) mechanisms shared by the four complexes. Two classes of key residues are distinguished in the Hsp70 ATPase domain: (i) highly conserved residues, involved in nucleotide binding, which mediate, via a global hinge-bending, the ATPase domain opening irrespective of NEF binding, and (ii) not-conserved but co-evolved and highly mobile residues, engaged in specific interactions with NEFs (e.g., N57, R258, R262, E283, D285). The observed interplay between these respective intrinsic (pre-existing, structure-encoded) and specific (co-evolved, sequence-dependent) interactions provides us with insights into the allosteric dynamics and functional evolution of the modular Hsp70 ATPase domain

Gender Imbalance in U.S. Geoscience Academia

Geoscientists explain women’s under-representation in our field along three dominant themes: the structure of academia, historically low numbers of women, and women’s views and choices. Which factor they perceive as most important depends overwhelmingly on their gender

The relationship between spatial distribution and diet of Arctic charr (Salvelinus alpinus) in Loch Ness, U.K.

The pelagic fish community of Loch Ness, U.K., is dominated by Arctic charr, Salvelinus alpinus. Previous studies have shown that the distribution of zooplankton along the south-west to north-east axis of this elongate loch is very dynamic and determined largely by prevailing winds, but Arctic charr are consistently more abundant in the southern half of the loch. In July 1993, the diet compositions of 161 Arctic charr from 53 to 330 mm in length were determined and related to their spatial distribution and those of microcrustacean zooplankton and pelagic chironomid larvae and pupae. Diets were dominated by chironomid larvae, with chironomid pupae, Bythotrephes longimanus, Bosmina coregoni and Daphnia hyalina also frequently taken. Over the whole study period, B. longimanus were more important in the diet of fish from the northern half of the loch, while chironomid larvae were more important for fish from the southern half. As a result, per capita prey weight of fish from the south was greater than that of fish from the north. However, wind-induced changes in the distribution of zooplankton along the loch were accompanied by a change in the diet composition of Arctic charr from the south