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
Department of Immunology, University of Texas Southwestern Medical Center, Dallas, United States.
Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, United States.
Elife. 2014 Jul 29;3:e03206. doi: 10.7554/eLife.03206.
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.
视黄醇在对感染的免疫反应中起着至关重要的作用，但在感染期间介导视黄醇运输的蛋白质尚未被鉴定出来。血清淀粉样蛋白A（SAA）在全身感染时在肝脏中强烈诱导产生，在细菌定植时在肠道中强烈诱导产生，但其确切功能仍不清楚。在这里，我们表明小鼠和人类的SAA是视黄醇结合蛋白。小鼠和人类的SAA以纳摩尔亲和力结合视黄醇，在体内与视黄醇相关联，并在急性感染后限制了组织中的细菌负荷。我们以2 Å的分辨率确定了小鼠SAA3的晶体结构，发现它形成了一个具有可容纳视黄醇的疏水结合口袋的四聚体。因此，我们的结果将SAA鉴定为一类微生物诱导的视黄醇结合蛋白，揭示了参与视黄醇结合的独特蛋白质结构，并提出了视黄醇在感染期间的循环方式。
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