Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection
- University of Texas Southwestern Medical Center, United States
- New York University School of Medicine, United States
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.
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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.
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.
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Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection
eLife 3:e03206.
https://doi.org/10.7554/eLife.03206
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