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

doi:10.7554/eLife.03206

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

Elife. 2014 Jul 29:3:e03206. doi: 10.7554/eLife.03206.

Authors

Mehabaw G Derebe¹, Clare M Zlatkov¹, Sureka Gattu¹, Kelly A Ruhn¹, Shipra Vaishnava¹, Gretchen E Diehl², John B MacMillan³, Noelle S Williams³, Lora V Hooper⁴

Affiliations

¹ Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States.
² Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, United States.
³ Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States.
⁴ Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States lora.hooper@utsouthwestern.edu.

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.

Keywords: acute phase response; crystal structure; retinol transport; serum amyloid A.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Biological Transport
Escherichia coli / genetics
Escherichia coli / metabolism
Gene Expression Regulation
Hep G2 Cells
Humans
Intestinal Mucosa / metabolism
Intestines / immunology
Intestines / microbiology
Kinetics
Liver / immunology
Liver / metabolism
Liver / microbiology
Mice
Mice, Inbred C57BL
Molecular Docking Simulation
Protein Multimerization
Protein Structure, Tertiary
Recombinant Proteins / chemistry
Recombinant Proteins / genetics
Recombinant Proteins / immunology
Retinol-Binding Proteins / chemistry*
Retinol-Binding Proteins / genetics
Retinol-Binding Proteins / immunology
Salmonella Infections / immunology
Salmonella Infections / metabolism*
Salmonella Infections / microbiology
Salmonella typhimurium / physiology
Serum Amyloid A Protein / chemistry*
Serum Amyloid A Protein / genetics
Serum Amyloid A Protein / immunology
Tissue Culture Techniques
Vitamin A / administration & dosage
Vitamin A / metabolism*

Substances

Recombinant Proteins
Retinol-Binding Proteins
Saa2 protein, mouse
Saa3 protein, mouse
Serum Amyloid A Protein
Vitamin A

Abstract

Publication types

MeSH terms

Substances

Grants and funding