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

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 exac...

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Autores principales: Derebe, Mehabaw G, Zlatkov, Clare M, Gattu, Sureka, Ruhn, Kelly A, Vaishnava, Shipra, Diehl, Gretchen E, MacMillan, John B, Williams, Noelle S, Hooper, Lora V
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4129439/
https://www.ncbi.nlm.nih.gov/pubmed/25073702
http://dx.doi.org/10.7554/eLife.03206
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author Derebe, Mehabaw G
Zlatkov, Clare M
Gattu, Sureka
Ruhn, Kelly A
Vaishnava, Shipra
Diehl, Gretchen E
MacMillan, John B
Williams, Noelle S
Hooper, Lora V
author_facet Derebe, Mehabaw G
Zlatkov, Clare M
Gattu, Sureka
Ruhn, Kelly A
Vaishnava, Shipra
Diehl, Gretchen E
MacMillan, John B
Williams, Noelle S
Hooper, Lora V
author_sort Derebe, Mehabaw G
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.03206.001
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spelling pubmed-41294392014-08-22 Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection Derebe, Mehabaw G Zlatkov, Clare M Gattu, Sureka Ruhn, Kelly A Vaishnava, Shipra Diehl, Gretchen E MacMillan, John B Williams, Noelle S Hooper, Lora V eLife Biophysics and Structural Biology 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. DOI: http://dx.doi.org/10.7554/eLife.03206.001 eLife Sciences Publications, Ltd 2014-07-29 /pmc/articles/PMC4129439/ /pubmed/25073702 http://dx.doi.org/10.7554/eLife.03206 Text en Copyright © 2014, Derebe et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biophysics and Structural Biology
Derebe, Mehabaw G
Zlatkov, Clare M
Gattu, Sureka
Ruhn, Kelly A
Vaishnava, Shipra
Diehl, Gretchen E
MacMillan, John B
Williams, Noelle S
Hooper, Lora V
Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection
title Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection
title_full Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection
title_fullStr Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection
title_full_unstemmed Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection
title_short Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection
title_sort serum amyloid a is a retinol binding protein that transports retinol during bacterial infection
topic Biophysics and Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4129439/
https://www.ncbi.nlm.nih.gov/pubmed/25073702
http://dx.doi.org/10.7554/eLife.03206
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