Modelling protein complexes with crosslinking mass spectrometry and deep learning
Open accessPreprint — published as 10.1038/s41467-024-51771-2
Abstract
Scarcity of structural and evolutionary information on protein complexes poses a challenge to deep learning-based structure modelling. We integrated experimental distance restraints obtained by crosslinking mass spectrometry (MS) into AlphaFold-Multimer, by extending AlphaLink to protein complexes. Integrating crosslinking MS data substantially improves modelling performance on challenging targets, by helping to identify interfaces, focusing sampling, and improving model selection. This extends to single crosslinks from whole-cell crosslinking MS, opening the possibility of whole-cell structural investigations driven by experimental data. We demonstrate this by revealing the molecular basis of iron homeostasis in Bacillus subtilis .
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Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Ahdritz, G., Bouatta, N., Floristean, C., Kadyan, S., Xia, Q., Gerecke, W., O’Donnell, T. J., Berenberg, D., Fisk, I., Zanichelli, N., et al. (2024) · Nature Methods · doi:10.1038/s41592-024-02272-z · Cited by 439 · see citing works
Functional specialization within the Fur family of metalloregulators
Lee, J.-W., & Helmann, J. D. (2007) · BioMetals · doi:10.1007/s10534-006-9070-7 · Cited by 432 · see citing works
Benchmarking AlphaFold for protein complex modeling reveals accuracy determinants
Yin, R., Feng, B. Y., Varshney, A., & Pierce, B. G. (2021) · doi:10.1101/2021.10.23.465575 · Cited by 335 · see citing works
Boyd, J. M., Esquilín-Lebrón, K., Campbell, C. J., Kaler, K. R., Norambuena, J., Foley, M. E., Stephens, T. G., Rios, G., Mereddy, G., Zheng, V., et al. (2023) · doi:10.1101/2023.10.03.560778 · Cited by 4 · see citing works
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- Authors
- Stahl, K., Demann, L., Bremenkamp, R., Warneke, R., Hormes, B., Stülke, J., Brock, O., & Rappsilber, J.
- Affiliations
- Technische Universität Berlin (DE)
- Wellcome Centre for Cell Biology (GB)
- Corresponding author
- Rappsilber, Juri
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2023-06-09
- OpenAlex
- W4379966111
- Cited by
- 20
- References
- 5
- Citations by year
- 2025: 2 · 2024: 13 · 2023: 5
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Wellcome Trust (227166, 203149)
- Deutsche Forschungsgemeinschaft (390540038, EXC 2002/1, 203149, 390523135, EXC 2002, EXC 2008)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Keywords
- protein complexes, cross-linking mass spectrometry, AlphaFold-Multimer, distance restraints, protein-protein interfaces, iron homeostasis, Bacillus subtilis
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