ArticleProceedings of the National Academy of Sciences of the United States of America2021
Targeted in situ cross-linking mass spectrometry and integrative modeling reveal the architectures of three proteins from SARS-CoV-2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 52 citations in OpenAlex.
- Coronavirus genome packaging and nucleocapsid assembly.Journal of virology · 2026Review
- Structural adaptability of SARS-CoV-2 Nsp1 with the host network.European biophysics journal : EBJ · 2026Article
- Deciphering a mechanistic basis for the pathological effect of the GNAO1 E246K variant in neurodevelopmental disorder.BBA advances · 2026Article
- State-of-the-Art and Future Directions in Structural Proteomics.Molecular & cellular proteomics : MCP · 2025Review
- Effects of Chemical Cross-Linking on the Structure of Proteins and Protein Assemblies.Analytical chemistry · 2025Article
- The differential effect of SARS-CoV-2 NSP1 on mRNA translation and stability reveals new insights linking ribosome recruitment, codon usage, and virus evolution.Nucleic acids research · 2025Article
- Frontiers in integrative structural modeling of macromolecular assemblies.QRB discovery · 2025Review
- An integrated approach using proximity labelling and chemical crosslinking to probeQRB discovery · 2024Review
- Applications of Mass Spectrometry in the Characterization, Screening, Diagnosis, and Prognosis of COVID-19.Advances in experimental medicine and biology · 2024Article
- All-in-One Pseudo-MSJournal of the American Society for Mass Spectrometry · 2023Article
- Protein Structure Prediction: Challenges, Advances, and the Shift of Research Paradigms.Genomics, proteomics & bioinformatics · 2023Review
- New advances in cross-linking mass spectrometry toward structural systems biology.Current opinion in chemical biology · 2023Review
- Hybrid structural modeling of alloantibody binding to human leukocyte antigen with rapid and reproducible cross-linking mass spectrometry.Cell reports methods · 2023Article
- Biochemical and HDX Mass Spectral Characterization of the SARS-CoV-2 Nsp1 Protein.Biochemistry · 2023Article
- All Domains of SARS-CoV-2 nsp1 Determine Translational Shutoff and Cytotoxicity of the Protein.Journal of virology · 2023Article
- Cross-linking mass spectrometry for mapping protein complex topologies in situ.Essays in biochemistry · 2023Article
- Atlas of interactions between SARS-CoV-2 macromolecules and host proteins.Cell insight · 2023Article
- An Outlook on Dental Practices to Avoid the Oral Transmission of COVID-19.Microorganisms · 2023Review
- The SARS-CoV-2 protein NSP2 impairs the silencing capacity of the human 4EHP-GIGYF2 complex.iScience · 2022Article
- Methodology-Centered Review of Molecular Modeling, Simulation, and Prediction of SARS-CoV-2.Chemical reviews · 2022Review
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Atomic structures of several proteins from the coronavirus family are still partial or unavailable. A possible reason for this gap is the instability of these proteins outside of the cellular context, thereby prompting the use of in-cell approaches. In situ cross-linking and mass spectrometry (in situ CLMS) can provide information on the structures of such proteins as they occur in the intact cell. Here, we applied targeted in situ CLMS to structurally probe Nsp1, Nsp2, and nucleocapsid (N) proteins from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and obtained cross-link sets with an average density of one cross-link per 20 residues. We then employed integrative modeling that computationally combined the cross-linking data with domain structures to determine full-length atomic models. For the Nsp2, the cross-links report on a complex topology with long-range interactions. Integrative modeling with structural prediction of individual domains by the AlphaFold2 system allowed us to generate a single consistent all-atom model of the full-length Nsp2. The model reveals three putative metal binding sites and suggests a role for Nsp2 in zinc regulation within the replication-transcription complex. For the N protein, we identified multiple intra- and interdomain cross-links. Our integrative model of the N dimer demonstrates that it can accommodate three single RNA strands simultaneously, both stereochemically and electrostatically. For the Nsp1, cross-links with the 40S ribosome were highly consistent with recent cryogenic electron microscopy structures. These results highlight the importance of cellular context for the structural probing of recalcitrant proteins and demonstrate the effectiveness of targeted in situ CLMS and integrative modeling.
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