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Methods that allow the study of the structure of proteins in complex with nanomaterials promise to enhance our understanding of how biological molecules interface with inorganic materials. We used single-particle cryo-electron microscopy (cryo-EM) to demonstrate the potential for cryo-EM analysis to reveal structural details of protein-nanoparticle complexes. Two protein-nanomaterial complexes, namely, GroEL bound to platinum nanoparticles (GroEL-PtNP) and ferritin bound to an iron oxide nanoparticle, were used as model samples. For the GroEL-PtNP complex, a final reconstruction was obtained to 3.93 Å, which allowed us to fit the atomic model of GroEL into the resulting map. This sets the stage for future work and improvements on the use of cryo-EM for the study of protein-nanomaterial complexes.
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http://dx.doi.org/10.1021/acsabm.2c00130 | DOI Listing |
Proc Natl Acad Sci U S A
September 2025
Martin A. Fisher School of Physics, Brandeis University, Waltham, MA 02453.
Programmable self-assembly has recently enabled the creation of complex structures through precise control of the interparticle interactions and the particle geometries. Targeting ever more structurally complex, dynamic, and functional assemblies necessitates going beyond the design of the structure itself, to the measurement and control of the local flexibility of the intersubunit connections and its impact on the collective mechanics of the entire assembly. In this study, we demonstrate a method to infer the mechanical properties of multisubunit assemblies using cryogenic electron microscopy (cryo-EM) and RELION's multi-body refinement.
View Article and Find Full Text PDFActa Crystallogr F Struct Biol Commun
October 2025
Science and Technology Facilities Council, Research Complex at Harwell, Didcot OX11 0FA, United Kingdom.
Ease of access to data, tools and models expedites scientific research. In structural biology there are now numerous open repositories of experimental and simulated data sets. Being able to easily access and utilize these is crucial to allow researchers to make optimal use of their research effort.
View Article and Find Full Text PDFActa Crystallogr D Struct Biol
October 2025
Centro Nacional de Biotecnologia-CSIC, Calle Darwin 3, 28049 Cantoblanco, Madrid, Spain.
Heterogeneity in cryoEM is essential for capturing the structural variability of macromolecules, reflecting their functional states and biological significance. However, estimating heterogeneity remains challenging due to particle misclassification and algorithmic biases, which can lead to reconstructions that blend distinct conformations or fail to resolve subtle differences. Furthermore, the low signal-to-noise ratio inherent in cryo-EM data makes it nearly impossible to detect minute structural changes, as noise often obscures subtle variations in macromolecular projections.
View Article and Find Full Text PDFJ Med Chem
September 2025
Repare Therapeutics, 7171 Frederick-Banting, Building 2, H4S 1Z9 Montréal, Québec, Canada.
DNA polymerase theta (Polθ) plays a critical role in repairing DNA double-strand breaks through microhomology-mediated end joining (MMEJ) and has emerged as a key synthetic lethal drug target in cancers with homologous recombination (HR) deficiencies. Its inhibition has shown a strong potential to synergize with PARP inhibitors, particularly in tumors with deleterious or mutations. Here, we describe the discovery and preclinical development of RP-2119, a selective, potent, and bioavailable Polθ ATPase inhibitor.
View Article and Find Full Text PDFProtein Cell
September 2025
Department of Human Cell Biology and Genetics, SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China.
Breast cancer is a prevalent malignancy worldwide. The majority of breast cancers belong to the estrogen receptor (ER)-positive luminal subtype that can be effectively treated with antiestrogen therapies. However, a significant portion of such malignancies become hormone-refractory and incurable.
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