Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Evolution of multifunctionality through a pleiotropic substitution in the innate immune protein S100A9

View ORCID ProfileJoseph L. Harman, Andrea N. Loes, Gus D. Warren, Maureen C. Heaphy, View ORCID ProfileKirsten J. Lampi, View ORCID ProfileMichael J. Harms
doi: https://doi.org/10.1101/865493
Joseph L. Harman
1Department of Chemistry and Biochemistry, University of Oregon, Eugene, OR, United States
2Institute of Molecular Biology, University of Oregon, Eugene, OR, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Joseph L. Harman
Andrea N. Loes
1Department of Chemistry and Biochemistry, University of Oregon, Eugene, OR, United States
2Institute of Molecular Biology, University of Oregon, Eugene, OR, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gus D. Warren
1Department of Chemistry and Biochemistry, University of Oregon, Eugene, OR, United States
2Institute of Molecular Biology, University of Oregon, Eugene, OR, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maureen C. Heaphy
1Department of Chemistry and Biochemistry, University of Oregon, Eugene, OR, United States
2Institute of Molecular Biology, University of Oregon, Eugene, OR, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kirsten J. Lampi
3Oregon Health & Science University, Portland, Oregon 97239, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Kirsten J. Lampi
Michael J. Harms
1Department of Chemistry and Biochemistry, University of Oregon, Eugene, OR, United States
2Institute of Molecular Biology, University of Oregon, Eugene, OR, United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Michael J. Harms
  • For correspondence: harms@uoregon.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

ABSTRACT

Multifunctional proteins are evolutionary puzzles: how do proteins evolve to satisfy multiple functional constraints? S100A9 is one such multifunctional protein. It potently amplifies inflammation via Toll-like receptor 4 and is antimicrobial as part of a heterocomplex with S100A8. These two functions are seemingly regulated by proteolysis: S100A9 is readily degraded, while S100A8/S100A9 is resistant. We take an evolutionary biochemical approach to show that S100A9 evolved both functions and lost proteolytic resistance from a weakly proinflammatory, proteolytically resistant amniote ancestor. We identify a historical substitution that has pleiotropic effects on S100A9 proinflammatory activity and proteolytic resistance but has little effect on S100A8/S100A9 antimicrobial activity. We thus propose that mammals evolved S100A8/S100A9 antimicrobial and S100A9 proinflammatory activities concomitantly with a proteolytic “timer” to selectively regulate S100A9. This highlights how the same mutation can have pleiotropic effects on one functional state of a protein but not another, thus facilitating the evolution of multifunctionality.

Footnotes

  • Funding sources: This research was funded by grants from the American Heart Association (AHA16 15BGIA22830013, MJH) and the National Institutes of Health (NIH-3R01GM117140-03S1, MJH; NIH-T32GM007413, JLH, ANL). MJH is a Pew Scholar in the Biomedical Sciences, supported by The Pew Charitable Trusts. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted December 05, 2019.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Evolution of multifunctionality through a pleiotropic substitution in the innate immune protein S100A9
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Evolution of multifunctionality through a pleiotropic substitution in the innate immune protein S100A9
Joseph L. Harman, Andrea N. Loes, Gus D. Warren, Maureen C. Heaphy, Kirsten J. Lampi, Michael J. Harms
bioRxiv 865493; doi: https://doi.org/10.1101/865493
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Evolution of multifunctionality through a pleiotropic substitution in the innate immune protein S100A9
Joseph L. Harman, Andrea N. Loes, Gus D. Warren, Maureen C. Heaphy, Kirsten J. Lampi, Michael J. Harms
bioRxiv 865493; doi: https://doi.org/10.1101/865493

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Biochemistry
Subject Areas
All Articles
  • Animal Behavior and Cognition (2513)
  • Biochemistry (4957)
  • Bioengineering (3456)
  • Bioinformatics (15148)
  • Biophysics (6868)
  • Cancer Biology (5365)
  • Cell Biology (7692)
  • Clinical Trials (138)
  • Developmental Biology (4509)
  • Ecology (7117)
  • Epidemiology (2059)
  • Evolutionary Biology (10193)
  • Genetics (7494)
  • Genomics (9758)
  • Immunology (4808)
  • Microbiology (13153)
  • Molecular Biology (5114)
  • Neuroscience (29321)
  • Paleontology (203)
  • Pathology (833)
  • Pharmacology and Toxicology (1458)
  • Physiology (2123)
  • Plant Biology (4723)
  • Scientific Communication and Education (1004)
  • Synthetic Biology (1336)
  • Systems Biology (3997)
  • Zoology (768)