The Saccharomyces cerevisiae (Sc) R2TP complex affords an Hsp90-mediated and nucleotide-driven chaperone activity to proteins of small ribonucleoprotein particles (snoRNPs). The current lack of structural information on the ScR2TP complex, however, prevents a mechanistic understanding of this biological process. We characterized the structure of the ScR2TP complex made up of two AAA+ ATPases, Rvb1/2p, and two Hsp90 binding proteins, Tah1p and Pih1p, and its interaction with the snoRNP protein Nop58p by a combination of analytical ultracentrifugation, isothermal titration calorimetry, chemical crosslinking, hydrogen-deuterium exchange, and cryoelectron microscopy methods. We find that Pih1p-Tah1p interacts with Rvb1/2p cooperatively through the nucleotide-sensitive domain of Rvb1/2p. Nop58p further binds Pih1p-Tahp1 on top of the dome-shaped R2TP. Consequently, nucleotide binding releases Pih1p-Tah1p from Rvb1/2p, which offers a mechanism for nucleotide-driven binding and release of snoRNP intermediates.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625358 | PMC |
| http://dx.doi.org/10.1016/j.str.2017.08.002 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Structural insights into the coupling between VCP, an essential unfoldase, and a deubiquitinase.
J Cell Biol
May 2025
Laboratory of Chemistry and Cell Biology, The Rockefeller University, New York, NY, USA.
Proteostasis involves degradation and recycling of proteins from organelles, membranes, and multiprotein complexes. These processes can depend on protein extraction and unfolding by the essential mechanoenzyme valosin-containing protein (VCP) and on ubiquitin chain remodeling by ubiquitin-specific proteases known as deubiquitinases (DUBs). How the activities of VCP and DUBs are coordinated is poorly understood.
View Article and Find Full Text PDFTrypanosome doublet microtubule structures reveal flagellum assembly and motility mechanisms.
Science
March 2025
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, USA.
The flagellum of drives the parasite's characteristic screw-like motion and is essential for its replication, transmission, and pathogenesis. However, the molecular details of this process remain unclear. Here, we present high-resolution (up to 2.
View Article and Find Full Text PDFEvolutionary adaptations of doublet microtubules in trypanosomatid parasites.
Science
March 2025
Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
The movement and pathogenicity of trypanosomatid species, the causative agents of trypanosomiasis and leishmaniasis, are dependent on a flagellum that contains an axoneme of dynein-bound doublet microtubules (DMTs). In this work, we present cryo-electron microscopy structures of DMTs from two trypanosomatid species, and , at resolutions up to 2.7 angstrom.
View Article and Find Full Text PDFFcrX coordinates cell cycle and division during free-living growth and symbiosis by a ClpXP-dependent mechanism.
Proc Natl Acad Sci U S A
March 2025
Commissariat à l'énergie atomique et aux énergies alternatives, CNRS, Institute for Integrative Biology of the Cell, Université Paris-Saclay, Gif-sur-Yvette 91198, France.
is a soil bacterium that establishes a nitrogen-fixing symbiosis within root nodules of legumes. In this symbiosis, undergoes a drastic cellular change leading to a terminally differentiated form, called bacteroid, characterized by genome endoreduplication, increased cell size, and high membrane permeability. Bacterial cell cycle (mis)regulation is at the heart of this differentiation process.
View Article and Find Full Text PDFThe deubiquitinase USP45 inhibits autophagy through actin regulation by Coronin 1B.
J Cell Biol
May 2025
Institute of Biological Chemistry, Academia Sinica , Taipei, Taiwan.
The autophagy-lysosomal system comprises a highly dynamic and interconnected vesicular network that plays a central role in maintaining proteostasis and cellular homeostasis. In this study, we uncovered the deubiquitinating enzyme (DUB), dUsp45/USP45, as a key player in regulating autophagy and lysosomal activity in Drosophila and mammalian cells. Loss of dUsp45/USP45 results in autophagy activation and increased levels of V-ATPase to lysosomes, thus enhancing lysosomal acidification and function.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!