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 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.
authors: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States.
authors: Mehabaw G
authors: MG
authors: Derebe
authors: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States.
authors: Clare M
authors: CM
authors: Zlatkov
authors: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States.
authors: Sureka
authors: S
authors: Gattu
authors: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States.
authors: Kelly A
authors: KA
authors: Ruhn
authors: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States.
authors: Shipra
authors: S
authors: Vaishnava
authors: Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, United States.
authors: Gretchen E
authors: GE
authors: Diehl
authors: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States.
authors: John B
authors: JB
authors: MacMillan
authors: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States.
authors: Noelle S
authors: NS
authors: Williams
authors: 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.
authors: Lora V
authors: LV
authors: Hooper
mesh_terms: D000818:Animals; D001692:Biological Transport; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D007700:Kinetics; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D062105:Molecular Docking Simulation; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D012177:Retinol-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D012480:Salmonella Infections / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000502:physiology; D000685:Serum Amyloid A Protein / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D046509:Tissue Culture Techniques; D014801:Vitamin A / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; D012177:Retinol-Binding Proteins; C489995:Saa2 protein, mouse; C076498:Saa3 protein, mouse; D000685:Serum Amyloid A Protein; D014801:Vitamin A
keywords: acute phase response; crystal structure; retinol transport; serum amyloid A