1. Structural Biology and Molecular Biophysics
  2. Immunology and Inflammation
Download icon

Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection

  1. Mehabaw G Derebe
  2. Clare M Zlatkov
  3. Sureka Gattu
  4. Kelly A Ruhn
  5. Shipra Vaishnava
  6. Gretchen E Diehl
  7. John B MacMillan
  8. Noelle S Williams
  9. Lora V Hooper  Is a corresponding author
  1. University of Texas Southwestern Medical Center, United States
  2. New York University School of Medicine, United States
Research Article
  • Cited 63
  • Views 4,625
  • Annotations
Cite this article as: eLife 2014;3:e03206 doi: 10.7554/eLife.03206

Abstract

Retinol plays a vital role in the immune response to infection, yet proteins that mediate retinol transport during infection have not been identified. Serum amyloid A (SAA) proteins are strongly induced in the liver by systemic infection and in the intestine by bacterial colonization, but their exact functions remain unclear. Here we show that mouse and human SAAs are retinol binding proteins. Mouse and human SAAs bound retinol with nanomolar affinity, were associated with retinol in vivo, and limited the bacterial burden in tissues after acute infection. We determined the crystal structure of mouse SAA3 at a resolution of 2 Å, finding that it forms a tetramer with a hydrophobic binding pocket that can accommodate retinol. Our results thus identify SAAs as a family of microbe-inducible retinol binding proteins, reveal a unique protein architecture involved in retinol binding, and suggest how retinol is circulated during infection.

Article and author information

Author details

  1. Mehabaw G Derebe

    University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Clare M Zlatkov

    University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Sureka Gattu

    University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Kelly A Ruhn

    University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Shipra Vaishnava

    University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Gretchen E Diehl

    New York University School of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. John B MacMillan

    University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Noelle S Williams

    University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Lora V Hooper

    University of Texas Southwestern Medical Center, Dallas, United States
    For correspondence
    lora.hooper@utsouthwestern.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: Animal subjects research approved by all animal experiments were approved by the Institutional Animal Care and Research Advisory Committee at the University of Texas Southwestern Medical Center, and the approved animal protocol number is 2011-0197. The institutional guidelines for the care and use of laboratory animals were followed.

Reviewing Editor

  1. Fiona M Powrie, Oxford University, United Kingdom

Publication history

  1. Received: April 26, 2014
  2. Accepted: July 28, 2014
  3. Accepted Manuscript published: July 29, 2014 (version 1)
  4. Version of Record published: August 12, 2014 (version 2)

Copyright

© 2014, Derebe et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 4,625
    Page views
  • 581
    Downloads
  • 63
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

  1. Further reading

Further reading

    1. Computational and Systems Biology
    2. Structural Biology and Molecular Biophysics
    Lukas S Stelzl et al.
    Research Article Updated
    1. Structural Biology and Molecular Biophysics
    Jun-ichi Kishikawa et al.
    Research Article