@article{ee29bac163a846838e58751c20132252,
title = "Molecular basis for retinol binding by serum amyloid A during infection",
abstract = "Serum amyloid A (SAA) proteins are strongly induced in the liver by systemic infection and in the intestine by bacterial colonization. In infected mice, SAA proteins circulate in association with the vitamin A derivative retinol, suggesting that SAAs transport retinol during infection. Here we illuminate a structural basis for the retinol–SAA interaction. In the bloodstream of infected mice, most SAA is complexed with high-density lipoprotein (HDL). However, we found that the majority of the circulating retinol was associated with the small fraction of SAA proteins that circulate without binding to HDL, thus identifying free SAA as the predominant retinol-binding form in vivo. We then determined the crystal structure of retinol-bound mouse SAA3 at a resolution of 2.2 {\AA}. Retinol-bound SAA3 formed a novel asymmetric trimeric assembly that was generated by the hydrophobic packing of the conserved amphipathic helices α1 and α3. This hydrophobic packing created a retinol-binding pocket in the center of the trimer, which was confirmed by mutagenesis studies. Together, these findings illuminate the molecular basis for retinol transport by SAA proteins during infection.",
keywords = "Crystal structure, Immunity, Infection, Retinol, Vitamin A",
author = "Zehan Hu and Bang, {Ye Ji} and Ruhn, {Kelly A.} and Hooper, {Lora V.}",
note = "Funding Information: I-1874 (to L.V.H.), the Walter M. and Helen D. Bader Center for Research on Arthritis and Autoimmune Diseases (L.V.H.), and the Howard Hughes Medical Institute (L.V.H.). Y.-J.B. was supported by a Crohn{\textquoteright}s and Colitis Foundation of America Research Fellowship Award. Funding Information: Center at the Advanced Photon Source. Argonne is operated by UChicago Argonne, LLC, for the US Department of Energy, Office of Biological and Environmental Research under Contract DE-AC02-06CH11357. This work was supported by NIH Grant R01 DK070855 (to L.V.H.), Welch Foundation Grant Funding Information: We thank Dr. Ruth Gordillo, Preethi Csudae, and Duyen Do (UT Southwestern Metabolic Phenotyping Core) for mass spectrometry analysis of retinoids in biological samples and Shimadzu Scientific Instruments for the collaborative effort. Structures shown in this report were derived from work performed at Argonne National Laboratory, Structural Biology Center at the Advanced Photon Source. Argonne is operated by UChicago Argonne, LLC, for the US Department of Energy, Office of Biological and Environmental Research under Contract DE-AC02-06CH11357. This work was supported by NIH Grant R01 DK070855 (to L.V.H.), Welch Foundation Grant I-1874 (to L.V.H.), the Walter M. and Helen D. Bader Center for Research on Arthritis and Autoimmune Diseases (L.V.H.), and the Howard Hughes Medical Institute (L.V.H.). Y.-J.B. was supported by a Crohn?s and Colitis Foundation of America Research Fellowship Award. Publisher Copyright: {\textcopyright} 2019 National Academy of Sciences. All rights reserved.",
year = "2019",
month = sep,
day = "17",
doi = "10.1073/pnas.1910713116",
language = "English (US)",
volume = "116",
pages = "19077--19082",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "38",
}