Tag

Cryo Em

All articles tagged with #cryo em

science5 days ago•19 min saved

Single-building-block design yields versatile quasisymmetric protein nanocages

Researchers demonstrate de novo design of large, quasisymmetric protein cages built from a single building block. By leveraging spontaneous symmetry breaking, a parametric cage-design framework, and RoseTTAFold diffusion modelling (with ProteinMPNN for sequence design), they generate 3 ≤ T ≤ 36 cages containing 180–2,160 subunits and diameters from 68 to 220 nm. Cryo-EM confirms the structures and shows symmetry breaking across non-equivalent subunit positions, expanding the design space for one-component cages with potential for delivering biologics at large internal volumes.

via Nature|

#cryo-em #de-novo-design #protein-nanocages

science5 days ago•18 min saved

Designer miniproteins target GPCRs with high precision

Nature reports computational de novo design of miniproteins that bind G protein-coupled receptors (GPCRs) with high affinity, enabling both agonists for itch/pain receptors and antagonists for cancer, metabolic disorders, and migraine. Cryo-EM structures of five receptor–miniprotein complexes closely match the design models, validating the approach, and a designed chemokine receptor antagonist mobilizes hematopoietic stem and progenitor cells in vivo with fewer adverse effects than a clinically used drug.

via Nature|

#cryo-em #de-novo-design #gpcr

science6 days ago•25 min saved

Programmable quasisymmetric protein cages from two complementary building blocks

Nature reports a computational design strategy using geometric frustration to create two-component, quasisymmetric protein cages that assemble into sphere-like structures by embedding curvature-inducing pentagonal defects. By pairing complementary trimeric and dimeric blocks, the authors programmably control cage size from ~40 nm to >200 nm and mass from 2 to >50 MDa, comparable to viral capsids. The cages are functionalized for ribonucleoprotein cargo loading and cellular uptake, enabling studies of cargo delivery and size-dependent diffusion in cells. Data and code are publicly available (Zenodo, GitHub), underscoring a new route for biologics delivery and cell biology tools.

via Nature|

#cryo-em #de-novo-design #protein-cages

science21 days ago•5 min saved

MIT Scientist Uncovers Flexible Pathways in Ribosome Assembly

MIT biologist Joey Davis shows ribosome assembly is dynamic and can proceed via multiple pathways, not a fixed sequence. Using cryo-EM and the CryoDRGN neural-network approach, his work reveals diverse intermediate structures when assembly is blocked and aims to speed up data collection to improve AI-based protein-structure prediction.

via MIT News|

#cryo-em #cryodrgn #protein-synthesis

science1 month ago•11 min saved

Protons on a Spin: The Proton Motive Force Powers Bacteria’s Tiny Engine

The article describes how bacteria run on a proton motive force that powers the flagellar motor, a nanoscale engine at the base of the flagellum. Recent cryo-EM studies mapped the motor’s components—especially the C ring and its stators—revealing how protons drive rotation and how phosphorylation of CheY flips the motor to switch between running and tumbling, illustrating how proton energetics power core cellular processes and life’s physics-driven machinery.

via Quanta Magazine|

#bacterial-flagellar-motor #biophysics #cryo-em

science1 month ago•67 min saved

ThermoCas9: a methylation-sensitive CRISPR enzyme enabling epigenetic-aware editing

ThermoCas9 is a thermostable Cas9 whose activity is blocked by methylation of the PAM cytosine (5mC) in PAMs 5′-NNNNCGA-3′ or 5′-NNNNCCA-3′, restricting binding and cleavage to unmethylated sites. Cryo-EM structures of pre- and post-cleavage states reveal how PAM bases are recognized and why methylation prevents engagement. In human cells, unmethylated PAMs edit efficiently whereas methylated ones do not; a catalytically enhanced ThermoCas9 and optimized delivery methods boost editing at hypomethylated breast cancer loci ESR1 and GATA3, illustrating a new layer of precision for genome engineering and potential epigenetic screening applications.

via Nature|

#cryo-em #dna-methylation #methylation-sensitive-editing

science2 months ago•57 min saved

DNA twist drives CRISPR-Cas9 off-targeting, topology-guided activation

Negatively supercoiled DNA minicircles reveal that DNA topology promotes Cas9 binding and faster cleavage, with cryo-EM showing a 15 Å swing of the HNH domain toward the target strand and greater PAM-distal R-loop flexibility. The off-target structures OT1 and OT2 adapt via non-canonical base-pairing across the protospacer, enabling mismatches to be accommodated even in seed and distal regions; truncated guides retain activity under topology-induced stress. Collectively, the findings explain topology-driven off-target activity and offer design principles for high-fidelity Cas9 variants that consider DNA topology.

via Nature|

#crispr-cas9 #cryo-em #dna-topology

science2 months ago•49 min saved

Marburg virus glycoprotein engages NPC1 with a novel, high-affinity binding to boost entry

New cryo-EM structures of Marburg virus glycoprotein (MBV GP) in three states—unbound, NPC1-C bound, and nanobody-bound—reveal that MBV GP binds NPC1 with a distinct, higher-affinity orientation than Ebola GP, aided by a partially flexible glycan cap that blocks NPC1 only partially. NPC1 engagement induces substantial conformational changes in MBV GP that promote membrane fusion, explaining MBV GP’s markedly higher entry efficiency. A neutralizing nanobody, Nanosota-MB1, mimics NPC1 at the receptor-binding site and blocks NPC1 binding, neutralizing MBV pseudoviruses. Together, these findings illuminate MBV entry mechanisms and point to potential antiviral strategies targeting GP–NPC1 interactions and receptor-triggered transitions.

via Nature|

#cryo-em #glycoprotein #marburg-virus

science2 months ago•3 min saved

3D Blueprint of E. coli–Targeting Virus Bas63 Boosts Phage Therapy Prospects

Scientists released a high-resolution cryo-EM map of Bas63, a bacteriophage that infects E. coli, revealing how its tail and distinctive surface proteins enable infection and offering a framework to select and optimize phages for treating drug-resistant bacteria; the study also highlights deep evolutionary links between bacteriophages and herpesviruses and builds on prior viral-structure work by the same team.

via SciTechDaily|

#antibiotic-resistance #bacteriophage #cryo-em

science2 months ago•63 min saved

DICER's dual-pocket mechanism refines microRNA cleavage fidelity

Nature reports that human DICER uses two distinct 5′-end binding pockets (a G-favoured pocket promoting DC21 and a U-favoured pocket promoting DC22), and that RNA motifs like mWCU and YCR, along with coordinated dsRBD/PAZ domain motions, influence cleavage site selection. Massively parallel dicing assays and cryo-EM reveal how the 5′-nt identity can override or be overridden by motifs, driving precise but flexible processing of substrates and offering insights for shRNA design across species.

via Nature|

#5-end-pocket #cryo-em #dicer

science2 months ago•75 min saved

Cryo-EM maps reveal how influenza polymerase snatches caps from host transcripts

New cryo-EM structures show influenza polymerase (FluPol) binds a transcribing host Pol II–DSIF complex to perform cap snatching. The PA endonuclease sits near the Pol II RNA exit, DSIF stabilizes the interaction, and the capped RNA is channeled from the cap-binding domain to the endonuclease before cleavage. After cleavage, the 3′ end of the primer is directed toward FluPol’s polymerase active site, yielding a primer ready for transcription initiation in a state that resembles the pre-initiation complex. Mutations at FluPol–Pol II–DSIF interfaces reduce polymerase activity in cells, defining a three-step mechanism and a window during early transcription when cap snatching can occur. These findings clarify how host transcription is hijacked for viral mRNA synthesis and suggest targets for antiviral strategies.

via Nature|

#cap-snatching #cryo-em #dsif

science3 months ago•13 min saved

Broadly protective antibody blocks gammaherpesvirus gB fusion across genera

Researchers report Fab5, a broadly reactive antibody that targets a conserved epitope on gammaherpesvirus gB, enabling cross-genus neutralization; it provides protection against authentic virus challenges in mice, non-human primates, and humanized mice, and cryo-EM reveals the epitope is exposed in both pre- and post-fusion conformations, offering a path toward broad-spectrum gammaherpesvirus vaccines.

via Nature|

#cross-genus #cryo-em #fab5

health-and-medicine4 months ago•7 min saved

Statin Muscle Pain Linked to Calcium Leaks in Muscle Cells

Columbia University researchers report that certain statins, notably simvastatin, can bind to the ryanodine receptor in muscle cells and trigger a calcium leak, which weakens muscles or activates enzymes that degrade them, offering a possible explanation for statin-related pain and suggesting approaches such as designing safer statins or using drugs that block the calcium leak.

via ScienceDaily|

#calcium-leak #cryo-em #health-and-medicine

science5 months ago•5 min saved

New Insights into T Cell Receptor Activation Could Boost Cancer Immunotherapy

Scientists at Rockefeller University have discovered that T cell receptors behave like a jack-in-the-box, snapping open upon encountering an antigen, thanks to a native membrane environment recreated using nanodiscs. This new understanding could lead to improved cancer immunotherapies and vaccines by enabling more precise re-engineering of T cell responses.

via SciTechDaily|

#cancer #cryo-em #immunotherapy

science6 months ago•55 min saved

AI Advances in Antibody Design Accelerate Drug Development and Viral Defense

The article discusses a novel computational approach using RFdiffusion, fine-tuned on antibody structures, to design de novo antibodies and VHHs with atomic-level accuracy, targeting specific epitopes. The method enables the creation of antibodies with precise epitope targeting, validated by cryo-EM structures, and demonstrates potential for rapid therapeutic development, although current success rates are low and can be improved with advanced filtering techniques like AlphaFold3.

via Nature|

#antibody-design #cryo-em #de-novo-antibodies