DOI: 10.1073/pnas.090099097. High throughput protein fold identification by using experimental constraints derived from intramolecular cross-links and mass spectrometry

High throughput protein fold identification by using experimental constraints derived from intramolecular cross-links and mass spectrometry

10.1073/pnas.090099097

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

We have used intramolecular cross-linking, MS, and sequence threading to rapidly identify the fold of a model protein, bovine basic fibroblast growth factor (FGF)-2. Its tertiary structure was probed with a lysine-specific cross-linking agent, bis(sulfosuccinimidyl) suberate (BS 3 ). Sites of cross-linking were determined by tryptic peptide mapping by using time-of-flight MS. Eighteen unique intramolecular lysine (Lys-Lys) cross-links were identified. The assignments for eight cross-linked peptides were confirmed by using post source decay MS. The interatomic distance constraints were all consistent with the tertiary structure of FGF-2. These relatively few constraints, in conjunction with threading, correctly identified FGF-2 as a member of the β-trefoil fold family. To further demonstrate utility, we used the top-scoring homolog, IL-1β, to build an FGF-2 homology model with a backbone error of 4.8 Å (rms deviation). This method is fast, is general, uses small amounts of material, and is amenable to automation.

Bibliography

Young, M. M., Tang, N., Hempel, J. C., Oshiro, C. M., Taylor, E. W., Kuntz, I. D., Gibson, B. W., & Dollinger, G. (2000). High throughput protein fold identification by using experimental constraints derived from intramolecular cross-links and mass spectrometry. Proceedings of the National Academy of Sciences, 97(11), 5802â5806.

Authors 8

Malin M. Young (first)
Ning Tang (additional)
Judith C. Hempel (additional)
Connie M. Oshiro (additional)
Eric W. Taylor (additional)
Irwin D. Kuntz (additional)
Bradford W. Gibson (additional)
Gavin Dollinger (additional)

References 29 Referenced 391

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:44 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 5:31 p.m.)
Indexed	5 days, 9 hours ago (Aug. 23, 2025, 12:58 a.m.)
Issued	25 years, 3 months ago (May 16, 2000)
Published	25 years, 3 months ago (May 16, 2000)
Published Online	25 years, 3 months ago (May 16, 2000)
Published Print	25 years, 3 months ago (May 23, 2000)

Funders 0

None

BibTeX

@article{Young_2000, title={High throughput protein fold identification by using experimental constraints derived from intramolecular cross-links and mass spectrometry}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.090099097}, DOI={10.1073/pnas.090099097}, number={11}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Young, Malin M. and Tang, Ning and Hempel, Judith C. and Oshiro, Connie M. and Taylor, Eric W. and Kuntz, Irwin D. and Gibson, Bradford W. and Dollinger, Gavin}, year={2000}, month=may, pages={5802–5806} }

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