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

Mehabaw G. Derebe, Clare M. Zlatkov, Sureka Gattu, Kelly A. Ruhn, Shipra Vaishnava, Gretchen E. Diehl, John B. MacMillan, Noelle S. Williams, Lora V. Hooper

Research output: Contribution to journalArticle

50 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)e03206
JournaleLife
Volume3
DOIs
StatePublished - 2014

Fingerprint

Serum Amyloid A Protein
Retinol-Binding Proteins
Protein Transport
Vitamin A
Bacterial Infections
Infection
Liver
Intestines
Proteins
Crystal structure
Tissue

Keywords

  • acute phase response
  • crystal structure
  • retinol transport
  • serum amyloid A

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Derebe, M. G., Zlatkov, C. M., Gattu, S., Ruhn, K. A., Vaishnava, S., Diehl, G. E., ... Hooper, L. V. (2014). Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection. eLife, 3, e03206. https://doi.org/10.7554/eLife.03206

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.

In: eLife, Vol. 3, 2014, p. e03206.

Research output: Contribution to journalArticle

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. In: eLife. 2014 ; Vol. 3. pp. e03206.
@article{1d2e2d4dbf514db789087fb4427893eb,
title = "Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection",
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 {\AA}, 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.",
keywords = "acute phase response, crystal structure, retinol transport, serum amyloid A",
author = "Derebe, {Mehabaw G.} and Zlatkov, {Clare M.} and Sureka Gattu and Ruhn, {Kelly A.} and Shipra Vaishnava and Diehl, {Gretchen E.} and MacMillan, {John B.} and Williams, {Noelle S.} and Hooper, {Lora V.}",
year = "2014",
doi = "10.7554/eLife.03206",
language = "English (US)",
volume = "3",
pages = "e03206",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",

}

TY - JOUR

T1 - Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection

AU - Derebe, Mehabaw G.

AU - Zlatkov, Clare M.

AU - Gattu, Sureka

AU - Ruhn, Kelly A.

AU - Vaishnava, Shipra

AU - Diehl, Gretchen E.

AU - MacMillan, John B.

AU - Williams, Noelle S.

AU - Hooper, Lora V.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - acute phase response

KW - crystal structure

KW - retinol transport

KW - serum amyloid A

UR - http://www.scopus.com/inward/record.url?scp=84964312987&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964312987&partnerID=8YFLogxK

U2 - 10.7554/eLife.03206

DO - 10.7554/eLife.03206

M3 - Article

C2 - 25073702

AN - SCOPUS:84927694863

VL - 3

SP - e03206

JO - eLife

JF - eLife

SN - 2050-084X

ER -