與免疫反應相關的人的HIN-200家族包括4個成員,，分別為黑色瘤缺乏因子2（absent in melanoma 2，AIM2）,、MNDA,、干擾素誘導蛋白16 （interferon-inducible protein 16，IFI16）和IFIX,。其中,，AIM2和IFI16分別是誘導炎性體形成和干擾素生成的DNA受體。
2012年4月5日,，Immunity在線發(fā)表了美國國立健康研究院國家過敏癥與傳染病研究所（NIAID）等多家科研機構的一篇題為"Structures of the HIN Domain：DNA Complexes Reveal Ligand Binding and Activation Mechanisms of the AIM2 Inflammasome and IFI16 Receptor"的研究論文,，解析了HIN結構域：DNA復合體的晶體結構。
在天然免疫中,，DNA的識別對抗病毒和抗菌防御來說極為重要,。結構顯示， 通過帶正電的HIN結構域殘基和雙鏈DNA的糖-磷酸骨架之間的靜電吸引非特異性識別DNA序列,。 自我抑制狀態(tài)下,，分子內熱蛋白結構域和HIN結構域的復合體通過DNA的結合而分開， 這便于炎性體的裝配,。
這些發(fā)現(xiàn)為進一步理解天然信號復合體的裝配機制提供了依據(jù),。(生物谷Bioon.com)
doi.org/10.1016/j.immuni.2012.02.014
PMC:
PMID:
Structures of the HIN Domain：DNA Complexes Reveal Ligand Binding and Activation Mechanisms of the AIM2 Inflammasome and IFI16 Receptor
Tengchuan Jin1， Andrew Perry1,， Jiansheng Jiang1,， Patrick Smith1， James A. Curry1， Leonie Unterholzner2,， Zhaozhao Jiang3,， Gabor Horvath4， Vijay A. Rathinam3,， Ricky W. Johnstone6,， 7， Veit Hornung5,， Eicke Latz3,， 4， Andrew G. Bowie2,， Katherine A. Fitzgerald3,， T. Sam Xiao1， ,，
1 Structural Immunobiology Unit,， Laboratory of Immunology， National Institute of Allergy and Infectious Diseases,， National Institutes of Health,， Bethesda， MD 20892-0430,， USA
2 School of Biochemistry and Immunology,， Trinity Biomedical Sciences Institute， Trinity College Dublin,， Dublin 2,， Ireland
3 Division of Infectious Diseases and Immunology， University of Massachusetts Medical School,， Worcester,， MA 01605， USA
4 Institute of Innate Immunity,， University Hospitals,， University of Bonn， 53127 Bonn,， Germany
5 Unit for Clinical Biochemistry,， Institute for Clinical Chemistry and Pharmacology， University Hospitals,， University of Bonn,， 53127 Bonn， Germany
6 Gene Regulation Laboratory,， Cancer Therapeutics Program,， The Peter MacCallum Cancer Institute,， St. Andrews Place， East Melbourne 3002,， Victoria,， Australia
7 The Sir Peter MacCallum Department of Oncology， University of Melbourne,， Parkville 3054,， Victoria， Australia
Received 25 October 2011. Revised 23 December 2011. Accepted 9 February 2012. Available online 5 April 2012. Published online： April 5,， 2012.
Summary
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 domains in an autoinhibited state is liberated by DNA binding,， which may facilitate the assembly of inflammasomes along the DNA staircase. These findings provide mechanistic insights into dsDNA as the activation trigger and oligomerization platform for the assembly of large innate signaling complexes such as the inflammasomes.
