Author summary Blast, caused by the fungal pathogen Magnaporthe oryzae, is one of the world’s most devastating rice diseases. During infection, M. oryzae secretes a diverse set of molecules, known as ...

NMR spectroscopy and functional assays define a conserved tyrosine motif outside the canonical J-domain core of J-domain proteins. The motif stabilizes the fold, and its phosphomimetic perturbation dr...

Recent AI developments and what they mean for us Quick primer on general AI models* State-of-the-art in AI agent capabilities AI agents in biology (examples) Discussion - what does this mean for our r...

The European Research Council (ERC) has today announced the winners of its latest Starting Grant competition. The funding, worth €705 million in total, will go to 421 early-career researchers across E...

Author summary Parasitic nematodes infect billions of people and livestock worldwide, causing major health and economic burdens, while increasing resistance threatens current treatments. These parasit...

Advances in artificial intelligence, particularly in deep learning, are transforming the field of protein structure prediction. AlphaFold has emerged as a benchmark tool due to its remarkable ability ...

Universität Greifswald

Biology has clever ways to mask the effects of potentially harmful gene mutations. Scientists are investigating how this ‘buffering’ works — and how to exploit it.

Faster and cheaper experimental screening methods will democratize and accelerate the identification of high-affinity binders with biomedical applications. Here the authors present Cell-Free Two-Hybri...

The molecular chaperone Hsp90 is an abundant and essential homodimer that supports the stability and folding of hundreds of client proteins in cells. Its C-terminal domain (CTD) mediates dimerization and serves as a docking site for cochaperones bearing tetratricopeptide repeat (TPR) domains, which recognize the conserved MEEVD motif located at the end of an intrinsically disordered CTD tail. Despite its conservation, the structural role of this tail remains poorly understood. We investigated the conformational behavior of the yeast Hsp90 (yHsp90) CTD tail and its response to the binding of the TPR-containing PPIase cochaperone Cpr6. Using site-directed spin labeling with nitroxide and Gd(III) labels, we examined full-length yHsp90 (FL), isolated CTD (IsoC), and tail-truncated variants by double electron–electron resonance (DEER) and EPR spectroscopy. The CTD tails in IsoC and FL adopted distinct conformational ensembles, attributed to intramolecular interactions with the middle domain in FL. Cpr6 binding abolished these differences, indicating disruption of intramolecular tail contacts. In IsoC, the tail also stabilized an additional CTD conformation near the dimer interface that was absent in FL and was lost upon tail truncation, consistent with tail–CTD interactions observed by NMR. This population was reduced upon Cpr6 binding, shifting the IsoC conformational distribution toward that of FL. Additionally, this population was reduced in cellular environments and mimics. Together, our results demonstrate that the disordered CTD tail is an active structural element that modulates both its own conformational ensemble and CTD architecture, highlighting its potential functional relevance in the Hsp90 chaperone cycle.

Engler et al. define the Sgt1-specific domain as essential for the Sgt1 chaperone function in yeast. Through structural and biochemical analyses, they uncover unique interactions of Sgt1 with Hsp90 and client proteins that enhance client maturation efficiency. Sgt1 stabilizes Hsp90-client complexes by preventing their dissociation mediated by the co-chaperone Aha1.

Disease-causing proteins – ERC Synergy Grant for research at TUM on the role of chaperone “helper proteins.”

Universität Greifswald

Abstract. Biogenesis of small interfering RNAs (siRNA) in Drosophila melanogaster involves the processing of double-stranded RNA (dsRNA) by Dcr-2 with Loqs