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
Affiliations
Mehabaw G Derebe
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States
Clare M Zlatkov
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States
Sureka Gattu
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States
Kelly A Ruhn
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States
Shipra Vaishnava
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States
Gretchen E Diehl
Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, United States
John B MacMillan
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
Noelle S Williams
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States
Lora V Hooper
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
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.
