Artificial intelligence reveals nuclear pore complexity
Open accessPreprint — published as 10.1126/science.abm9506 · Paper page
Abstract
Nuclear pore complexes (NPCs) mediate nucleocytoplasmic transport. Their intricate 120 MDa architecture remains incompletely understood. Here, we report a near-complete structural model of the human NPC scaffold with explicit membrane and in multiple conformational states. We combined AI-based structure prediction with in situ and in cellulo cryo-electron tomography and integrative modeling. We show that linker Nups spatially organize the scaffold within and across subcomplexes to establish the higher-order structure. Microsecond-long molecular dynamics simulations suggest that the scaffold is not required to stabilize the inner and outer nuclear membrane fusion, but rather widens the central pore. Our work exemplifies how AI-based modeling can be integrated with in situ structural biology to understand subcellular architecture across spatial organization levels. One sentence summary: An AI-based, dynamic model of the human nuclear pore complex reveals how the protein scaffold and the nuclear envelope are coupled inside cells.
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ColabFold - Making protein folding accessible to all
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- Authors
- Mosalaganti, S., Obarska-Kosinska, A., Siggel, M., Turonova, B., Zimmerli, C. E., Buczak, K., Schmidt, F. H., Margiotta, E., Mackmull, M.-T., Hagen, W., Hummer, G., Beck, M., & Kosinski, J.
- Affiliations
- University of Michigan (US)
- Max Planck Institute of Biophysics (DE)
- European Molecular Biology Laboratory (DE)
- Goethe University Frankfurt (DE)
- Corresponding author
- Mosalaganti, Shyamal
- Siggel, Marc
- Hummer, Gerhard
- Beck, Martin
- ORCID
- Venue
- Science
- Publisher
- openRxiv
- Published
- 2021-10-27
- Volume
- 376
- Issue
- 6598
- Pages
- eabm9506-eabm9506
- ISSN
- 0036-8075 (ISSN-L)
- OpenAlex
- W4282936228
- Cited by
- 355
- References
- 2
- Citations by year
- 2026: 55 · 2025: 81 · 2024: 80 · 2023: 85 · 2022: 51 · 2021: 2 · 2012: 1
- FWCI
- 24.25
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Science (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Desy Publications Database (Deutsches Elektronen-Synchrotron DESY) (publishedVersion)
- Institute of Science and Technology Austria (submittedVersion)
- Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by-nc-nd)
- Funders
- European Molecular Biology Laboratory
- Bundesministerium für Bildung und Forschung (FKZ 031L0100)
- Max-Planck-Gesellschaft
- H2020 European Research Council (724349)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- nuclear pore complex, nucleoporins, integrative structural modeling, scaffold architecture, intrinsically disordered proteins, conformational dynamics, nuclear transport, nuclear envelope, protein-protein interaction network
- MeSH terms
- Artificial Intelligence, Humans, Cryoelectron Microscopy, Active Transport, Cell Nucleus, Nuclear Pore, Nuclear Pore Complex Proteins, Proteomics, Molecular Dynamics Simulation
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