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Cryo Em

All articles tagged with #cryo em

DNA twist drives CRISPR-Cas9 off-targeting, topology-guided activation
science15 days ago

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
Marburg virus glycoprotein engages NPC1 with a novel, high-affinity binding to boost entry
science1 month ago

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
3D Blueprint of E. coli–Targeting Virus Bas63 Boosts Phage Therapy Prospects
science1 month ago

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
DICER's dual-pocket mechanism refines microRNA cleavage fidelity
science1 month ago

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
Cryo-EM maps reveal how influenza polymerase snatches caps from host transcripts
science1 month ago

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
science2 months ago

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
Statin Muscle Pain Linked to Calcium Leaks in Muscle Cells
health-and-medicine2 months ago

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
New Insights into T Cell Receptor Activation Could Boost Cancer Immunotherapy
science3 months ago

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
AI Advances in Antibody Design Accelerate Drug Development and Viral Defense
science5 months ago

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
Revealing the Ultrafast Calcium Transport Mechanism of Plasma Membrane Ca2+-ATPases
biology7 months ago

Revealing the Ultrafast Calcium Transport Mechanism of Plasma Membrane Ca2+-ATPases

This article explores the molecular structure and function of plasma membrane Ca2+-ATPases (PMCAs), revealing how they achieve ultrafast calcium transport through specific structural features, interactions with phospholipids like PtdIns(4,5)P2, and conformational changes during their transport cycle, with implications for understanding their role in cellular calcium signaling and potential drug targeting.

via Nature|
#biology#ca2-atpases#cryo-em
"Bacterial Flagellum: Unveiling the Structural Basis of Directional Switching"
science2 years ago

"Bacterial Flagellum: Unveiling the Structural Basis of Directional Switching"

Researchers have used cryo-electron microscopy (cryo-EM) to investigate the structural basis of directional switching by the bacterial flagellum, a molecular motor that propels bacteria. The study provides atomic-level insights into the mechanisms underlying the ability of the flagellum to change direction, shedding light on the complex molecular machinery involved in this process. The data and code used for the analysis are publicly available, and the findings contribute to our understanding of bacterial motility and could have implications for the development of novel antimicrobial strategies.

via Nature.com|
#bacterial-flagellum#cryo-em#directional-switching