Cryo-EM Ribosome Analysis Service
You may currently be encountering challenges such as prolonged drug development cycles or difficulties in obtaining high-resolution structural data for complex protein targets. Our cryo-EM ribosome analysis service development helps you accelerate drug discovery by obtaining high-resolution structural information for the most complex targets. We use advanced cryo-EM technology to overcome the limitations of traditional methods.
Service Outline
The ribosome is a massive, multi-subunit macromolecular machine responsible for protein synthesis in all living organisms. Its complex and dynamic nature makes it an ideal, yet challenging, target for structural analysis. The use of cryo-EM has been a revolutionary breakthrough in this field, allowing scientists to bypass the need for crystallization and obtain high-resolution structures of the ribosome and its associated factors in various functional states. This technology provides a new frontier for understanding fundamental biological processes and for developing targeted antibacterial therapeutics that inhibit protein synthesis.
Fig.1 Cryo-EM structure of the 11-2F-bound PRMT5:MEP50 complex.1
Workflow
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Project Assessment & Design
Our expert team reviews your project's specific goals, challenges, and starting materials to design a tailored cryo-EM strategy. -
Sample Preparation & Screening
Your sample is prepared for cryo-EM imaging. A rapid negative-stain screening step is performed to assess sample quality and ensure particle uniformity before moving to cryogenic preparation.
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Data Collection
Using cutting-edge electron microscopes, we collect thousands of high-resolution 2D images of the vitrified particles from various angles.
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Data Processing & 3D Reconstruction
The raw image data is computationally processed to align and average the particles, leading to a high-resolution 3D density map of your target.
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Atomic Model Building & RefinementAn atomic model of the ribosome-ligand complex is built into the 3D map, and the structure is refined to provide atomic-level detail.
Applications
- Accelerating Antibiotic Discovery
Many antibiotics target bacterial ribosomes, but resistance is rising. cryo-EM structures of ribosome-antibiotic complexes reveal binding sites, allosteric effects, and resistance mutations. By analyzing pathogen-specific ribosomes, we identify selective inhibitors that spare human mitochondria, reducing toxicity.
- Probing Evolutionary Adaptations in Ribosomes
Ribosomes vary widely across life, from extremophiles to organelles. cryo-EM uncovers structural innovations, such as simplified mitochondrial ribosomes or parasite-specific rRNA expansions in Plasmodium.
- Structure-Based Drug Screening for Ribosomal Targets
cryo-EM enables fragment-based screening by directly visualizing small molecules bound to ribosomal pockets. Our pipeline identifies lead compounds with novel scaffolds, prioritizing hits for medicinal chemistry.
- Supporting Synthetic Biology
cryo-EM validates engineered ribosomes with altered substrate specificities or drug resistance, ensuring functionality before deployment.
Core Highlights
- Ultra-High Resolution Structural Insights
Our cryo-EM ribosome analysis delivers near-atomic resolution, enabling precise visualization of ribosomal subunits, active sites, and ligand interactions. This level of detail is critical for understanding translation mechanisms, antibiotic binding modes, and disease-related mutations. By leveraging cutting-edge microscopes and advanced image processing, we uncover structural features invisible to traditional techniques, empowering your research with unparalleled clarity.
- Rapid Turnaround
We prioritize efficiency without sacrificing accuracy. Our streamlined workflow, from sample preparation to data processing, ensures results in weeks, not months. With dedicated experts optimizing every step, including automated particle picking and 3D reconstruction, we accelerate your project timeline while maintaining the highest quality standards. Ideal for time-sensitive drug discovery or structural biology milestones.
- Comprehensive Sample Flexibility
From native ribosomes to complex assemblies with ligands, mRNAs, or nascent chains, our platform accommodates diverse sample types. We specialize in challenging specimens, including low-abundance or heterogeneous complexes, using tailored cryo-plunging and grid optimization techniques. This versatility ensures your unique biological questions are addressed, whether studying bacterial, eukaryotic, or mitochondrial ribosomes.
- Expert-Led Data Interpretation
Beyond raw data, we provide actionable insights. Our team of structural biologists and biochemists translates cryo-EM maps into mechanistic models, highlighting functionally relevant regions and potential drug targets. Custom reports include interactive 3D visualizations, validation metrics, and comparative analyses with existing structures, enabling you to make informed decisions swiftly.
FAQs
Q: Why should I choose cryo-EM over X-ray crystallography for my ribosome project?
A: cryo-EM is particularly advantageous for large, dynamic, or difficult-to-crystallize complexes like the ribosome. It allows us to visualize the structure in a near-native state without the need for extensive and often unsuccessful crystallization trials, saving you significant time and resources.
Q: How much sample material is required for your cryo-EM service?
A: One of the key benefits of cryo-EM single-particle analysis is its low sample volume requirement. We can often achieve high-quality results with as little as a few hundred micrograms of purified material, which is a major advantage for projects with limited sample availability.
Q: Can your service analyze the binding of a small molecule to the ribosome?
A: Yes, our cryo-EM Ribosome Analysis Service is specifically designed for this. We can co-incubate your small molecule with the ribosome to determine the precise binding location and mechanism at an atomic level, providing the insights you need for lead optimization.
Q: How do you ensure the quality of the final structural data?
A: We follow a rigorous, multi-step workflow including negative staining screening, high-resolution data collection with state-of-the-art instruments, and advanced computational refinement. We also provide all raw data files and a detailed report, ensuring full transparency and reproducibility.
Q: How does this service compare to other structural analysis platforms?
A: Our comprehensive approach combines advanced technology with deep biological expertise. Unlike single-service providers, we can recommend and execute the most suitable technique for your specific project, whether it's cryo-EM, X-ray, or NMR, providing a truly holistic solution.
Creative Biolabs provides a powerful, integrated platform for solving the most challenging structural biology problems. Our cryo-EM ribosome analysis service is just one example of how we combine cutting-edge technology with unparalleled expertise to accelerate your research and guide your project toward success. From sample to final structure, we are committed to being your trusted partner in drug discovery. To discuss your project in detail and learn how our cryo-EM expertise can benefit you, please contact our team.
Reference
- Zhou, Wei, et al. "Cryo-EM structure-based selection of computed ligand poses enables design of MTA-synergic PRMT5 inhibitors of better potency." Communications Biology 5.1 (2022): 1054. DOI: 10.1038/s42003-022-03991-9. Distributed under Open Access license CC BY 4.0, without modification.
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