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A designed Zn 2+ sensor domain transmits binding information to transmembrane histidine kinases
Open accessPreprint — published as 10.1021/jacs.5c02273 · Paper page
Abstract
Generating stimulus-responsive, allosteric signaling de novo is a significant challenge in protein design. In natural systems like bacterial histidine kinases (HKs), signal transduction occurs when ligand binding initiates a signal that is amplified across biological membranes over long distances to induce large-scale rearrangements and phosphorylation relays. Here, we ask whether our understanding of protein design and multi-domain, intramolecular signaling has progressed sufficiently to enable engineering of a HK with tunable de novo components. We generated de novo metal-binding sensor domains and substituted them for the native sensor domain of a transmembrane HK, affording chimeras that transduce signals initiated from a de novo sensor. Signaling depended on the designed sensor’s stability and the interdomain linker’s phase and length. These results show the usefulness of de novo design to elucidate biochemical mechanisms and principles for design of new signaling systems.
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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
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Research works printed but not linked: 80
- 10.1016/j.sbi.2021.08.004 · DOI
- 10.1016/j.cell.2023.12.028 · DOI
- 10.1126/science.8346440 · DOI
- 10.1021/ja0543604 · DOI · Paper page
- 10.1126/science.1261172 · DOI
- 10.1126/science.aax8780 · DOI
- 10.1038/s41589-023-01463-7 · DOI
- 10.1038/s41467-021-25735-9 · DOI
- 10.1126/science.aav7897 · DOI
- 10.1038/s41586-019-1432-8 · DOI
- 10.1038/s41586-019-1425-7 · DOI
- 10.1126/science.adg7731 · DOI · Paper page
- 10.1038/s41586-021-03258-z · DOI · Paper page
- 10.1038/s41594-021-00649-8 · DOI
- 10.1126/science.1085945 · DOI
- 10.1016/j.sbi.2016.06.012 · DOI
- 10.1016/S0959-440X(02)00290-7 · DOI · Paper page
- 2015, Signal Transduction in Histidine Kinases: Insights from New Structures, Struct. Lond. Engl. 1993, 23, 981
- 10.1146/annurev.micro.112408.134054 · DOI
- 10.1146/annurev.biochem.69.1.183 · DOI
- 10.1186/gb-2002-3-reviews3013 · DOI
- 10.1146/annurev-biochem-091008-152423 · DOI
- 10.1371/journal.pbio.1001493 · DOI
- 10.1126/science.aah6345 · DOI
- Gushchin, I. et al. Sensor Histidine Kinase NarQ Activates via Helical Rotation, Diagonal Scissoring, and Eventually Piston-Like Shifts. Int. J. Mol. Sci. 21, (2020). · DOI
- 10.1038/s41579-018-0055-7 · DOI
- 10.1371/journal.pbio.1001776 · DOI
- 10.1016/j.str.2010.01.013 · DOI
- 10.1016/j.jbc.2024.107265 · DOI
- 10.1128/jb.00593-17 · DOI
- 10.1016/j.cell.2008.04.040 · DOI
- 10.1021/acssynbio.1c00090 · DOI
- 10.1016/j.jmb.2010.10.038 · DOI
- 10.1073/pnas.2218610120 · DOI
- 10.1126/science.2476847 · DOI
- 10.1038/nature04405 · DOI
- 10.1128/jb.176.4.1157-1163.1994 · DOI
- 10.1016/j.jmb.2008.12.017 · DOI
- 10.1038/s41467-024-49251-8 · DOI
- 10.1021/acssynbio.6b00028 · DOI
- 10.1021/jacs.7b08261 · DOI
- 10.1002/bies.20343 · DOI
- 10.1073/pnas.1104824108 · DOI
- 10.1073/pnas.0506961102 · DOI
- 10.1016/j.tim.2004.10.003 · DOI
- 10.1016/j.str.2012.02.021 · DOI
- 10.1074/jbc.M710592200 · DOI
- 10.1016/j.jmb.2008.01.024 · DOI
- 10.1016/j.str.2008.12.013 · DOI
- 10.1002/pro.2610 · DOI
- 10.1021/jacs.0c10136 · DOI
- 10.1002/pro.5560041202 · DOI
- 10.1110/ps.0201402 · DOI · Paper page
- 10.1073/pnas.91.8.3127 · DOI
- 10.1371/journal.ppat.1006533 · DOI
- 10.1021/bi301132k · DOI
- Clark, I. C. et al. Protein design-scapes generated by microfluidic DNA assembly elucidate domain coupling in the bacterial histidine kinase CpxA. Proc. Natl. Acad. Sci. 118, (2021). · DOI
- 10.7554/eLife.73336 · DOI
- 10.1074/jbc.M114.565762 · DOI
- 10.1016/j.str.2017.04.011 · DOI
- 10.1002/pro.3095 · DOI
- 10.15252/msb.20167416 · DOI
- 10.1021/acs.chemrev.5b00623 · DOI
- 10.1021/cr4005082 · DOI
- 10.1016/j.sbi.2020.01.017 · DOI
- 10.1016/j.sbi.2022.102334 · DOI
- 10.1038/S41586-024-07487-W · DOI · Paper page
- 10.1101/2024.10.10.615955 · DOI · Paper page
- 10.1074/jbc.M110.179150 · DOI
- 10.1128/JB.184.19.5468-5478.2002 · DOI
- 2014, Cys-scanning disulfide crosslinking and bayesian modeling probe the transmembrane signaling mechanism of the histidine kinase, PhoQ, Struct. Lond. Engl. 1993, 22, 1239
- 10.1126/science.abb8330 · DOI
- 10.1126/science.adl5364 · DOI
- 10.1101/2023.12.20.572602 · DOI
- 10.1101/2023.12.22.573103 · DOI
- 10.1101/2023.11.01.565201 · DOI · Paper page
- 10.1126/sci-ence.adl2528 · DOI
- 1999, Protein identification and analysis tools in the ExPASy server, Methods Mol. Biol. Clifton NJ, 112, 531
- 10.1016/j.jinorgbio.2015.08.024 · DOI
- 10.1073/pnas.120163297 · DOI
Metadata
- Authors
- Hatstat, A. K., Kormos, R., Xu, V., & DeGrado, W. F.
- Affiliations
- University of California, San Francisco (US)
- City College of San Francisco (US)
- Corresponding author
- Hatstat, A. Katherine
- DeGrado, William F.
- Venue
- Journal of the American Chemical Society
- Publisher
- openRxiv
- Published
- 2024-10-31
- Volume
- 147
- Issue
- 22
- Pages
- 18770-18782
- ISSN
- 0002-7863 (ISSN-L)
- PMC
- PMC11565981
- OpenAlex
- W4410495765
- Cited by
- 1
- References
- 1
- Citations by year
- 2026: 1
- FWCI
- 0.30
- Type
- journal article
- Language
- en
- Open access
- Locations
- Journal of the American Chemical Society (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- National Science Foundation (2108660, 2306190)
- National Natural Science Foundation of China (22177113)
- National Institutes of Health (1k99gm155611-01)
- National Defense Science and Engineering Graduate
- National Key Research and Development Program of China (2024YFA0916800)
- National Institute of General Medical Sciences (F32GM147962, K99 GM155611, R35GM122603)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- de novo protein design, allosteric communication, intramolecular signal transduction, fusion protein, interdomain linker
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