Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

STRUCTURAL BIOLOGY

Mutagenesis-based protein structure determination

Nature Genetics volume 51, pages 1072–1073 (2019)Cite this article

Subjects

Genetics has played a key role in understanding the relationship between the DNA sequence encoding a protein and the protein’s three-dimensional structure. Two new studies present similar analytical approaches to predict three-dimensional structure on the basis of genetic interaction data.

Recent advances in multiplex assays have enabled measurement of the effects of hundreds of thousands of protein mutants1,2. New work from the Lehner3 and Marks4 groups leverages these large-scale mutagenesis datasets to infer protein structures by taking advantage of unexpected functional effects when alterations occur near each other in the folded structure of the protein.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1

References

  1. Fowler, D. M. & Fields, S. Nat. Methods 11, 801–807 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Gasperini, M., Starita, L. & Shendure, J. Nat. Protoc. 11, 1782–1787 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Schmiedel, J. M. & Lehner, B. Nat. Genet. https://doi.org/10.1038/s41588-019-0431-x (2019).

  4. Rollins, N. J. et al. Nat. Genet. https://doi.org/10.1038/s41588-019-0432-9 (2019).

  5. Altschuh, D., Lesk, A. M., Bloomer, A. C. & Klug, A. J. Mol. Biol. 193, 693–707 (1987).

    Article  CAS  PubMed  Google Scholar 

  6. Miller, C. S. & Eisenberg, D. Bioinformatics 24, 1575–1582 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Marks, D. S., Hopf, T. A. & Sander, C. Nat. Biotechnol. 30, 1072–1080 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ovchinnikov, S. et al. eLife 4, e09248 (2015).

    PubMed  PubMed Central  Google Scholar 

  9. Sahoo, A., Khare, S., Devanarayanan, S., Jain, P. & Varadarajan, R. eLife 4, e09532 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Baryshnikova, A., Costanzo, M., Myers, C. L., Andrews, B. & Boone, C. Annu. Rev. Genom. Hum. Genet. 14, 111–133 (2013).

    Article  CAS  Google Scholar 

  11. Olson, C. A., Wu, N. C. & Sun, R. Curr. Biol. 24, 2643–2651 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Araya, C. L. et al. Proc. Natl Acad. Sci. USA 109, 16858–16863 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Diss, G. & Lehner, B. eLife 7, e32472 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Genome Sciences, University of Washington, Seattle, WA, USA

    Melissa Chiasson & Douglas M. Fowler

  2. Department of Bioengineering, University of Washington, Seattle, WA, USA

    Douglas M. Fowler

  3. Genetic Networks Program, CIFAR, Toronto, Ontario, Canada

    Douglas M. Fowler

Authors
  1. Melissa Chiasson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Douglas M. Fowler
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Douglas M. Fowler.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chiasson, M., Fowler, D.M. Mutagenesis-based protein structure determination. Nat Genet 51, 1072–1073 (2019). https://doi.org/10.1038/s41588-019-0461-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41588-019-0461-4

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing