Journal article
Structures of the HIN Domain: DNA Complexes Reveal Ligand Binding and Activation Mechanisms of the AIM2 Inflammasome and IFI16 Receptor
T Jin, A Perry, J Jiang, P Smith, JA Curry, L Unterholzner, Z Jiang, G Horvath, VA Rathinam, RW Johnstone, V Hornung, E Latz, AG Bowie, KA Fitzgerald, TS Xiao
Immunity | Published : 2012
Abstract
Recognition of DNA by the innate immune system is central to antiviral and antibacterial defenses, as well as an important contributor to autoimmune diseases involving self DNA. AIM2 (absent in melanoma 2) and IFI16 (interferon-inducible protein 16) have been identified as DNA receptors that induce inflammasome formation and interferon production, respectively. Here we present the crystal structures of their HIN domains in complex with double-stranded (ds) DNA. Non-sequence-specific DNA recognition is accomplished through electrostatic attraction between the positively charged HIN domain residues and the dsDNA sugar-phosphate backbone. An intramolecular complex of the AIM2 Pyrin and HIN doma..
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Awarded by Cancer Council Victoria
Funding Acknowledgements
We thank the beam line scientists at the Argonne National Laboratory GM/CA-CAT (Argonne, IL) and the Brookhaven National Laboratory (Upton, NY) for their support on data collection. The authors would like to thank A. Mian from LI, NIAID for technical support. We thank R. Schwartz, M. Lenardo, and D. Margulies for helpful discussions. We thank D.E. Anderson at the Mass Spectrometry facility of NIDDK for technical support. T.S.X. is supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH. A.G.B. and L.U. are supported by Science Foundation Ireland (07/IN1/B934). K.A.F. is supported by NIH grants AI083713 and AI067497. E.L. is supported by NIH grant AI067497. V.H. is supported by the European Research Council (ERC-2009-StG 243046) and the DFG (SFB704 and SFB670). R.W.J. is a Principal Research Fellow of the National Health and Medical Research Council of Australia (NHMRC) and supported by NHMRC Program and Project Grants, the Susan G. Komen Breast Cancer Foundation, the Prostate Cancer Foundation of Australia, Cancer Council Victoria, The Leukemia Foundation of Australia, Victorian Breast Cancer Research Consortium, and Victorian Cancer Agency. V.A.R. is supported by a NERCE Postdoctoral fellowship.