Home > Research > Publications & Outputs > Structures of the HIN domain:DNA complexes reve...

Links

Text available via DOI:

View graph of relations

Structures of the HIN domain:DNA complexes reveal ligand binding and activation mechanisms of the AIM2 inflammasome and IFI16 receptor

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Published

Standard

Structures of the HIN domain:DNA complexes reveal ligand binding and activation mechanisms of the AIM2 inflammasome and IFI16 receptor. / Jin, Tengchuan; Perry, Andrew; Jiang, Jiansheng et al.

In: Immunity, Vol. 36, No. 4, 20.04.2012, p. 561-571.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Jin, T, Perry, A, Jiang, J, Smith, P, Curry, JA, Unterholzner, L, Jiang, Z, Horvath, G, Rathinam, VA, Johnstone, RW, Hornung, V, Latz, E, Bowie, AG, Fitzgerald, KA & Xiao, TS 2012, 'Structures of the HIN domain:DNA complexes reveal ligand binding and activation mechanisms of the AIM2 inflammasome and IFI16 receptor', Immunity, vol. 36, no. 4, pp. 561-571. https://doi.org/10.1016/j.immuni.2012.02.014

APA

Jin, T., Perry, A., Jiang, J., Smith, P., Curry, J. A., Unterholzner, L., Jiang, Z., Horvath, G., Rathinam, V. A., Johnstone, R. W., Hornung, V., Latz, E., Bowie, A. G., Fitzgerald, K. A., & Xiao, T. S. (2012). Structures of the HIN domain:DNA complexes reveal ligand binding and activation mechanisms of the AIM2 inflammasome and IFI16 receptor. Immunity, 36(4), 561-571. https://doi.org/10.1016/j.immuni.2012.02.014

Vancouver

Jin T, Perry A, Jiang J, Smith P, Curry JA, Unterholzner L et al. Structures of the HIN domain:DNA complexes reveal ligand binding and activation mechanisms of the AIM2 inflammasome and IFI16 receptor. Immunity. 2012 Apr 20;36(4):561-571. doi: 10.1016/j.immuni.2012.02.014

Author

Jin, Tengchuan ; Perry, Andrew ; Jiang, Jiansheng et al. / Structures of the HIN domain:DNA complexes reveal ligand binding and activation mechanisms of the AIM2 inflammasome and IFI16 receptor. In: Immunity. 2012 ; Vol. 36, No. 4. pp. 561-571.

Bibtex

@article{e88eb22e10e24763990da7b2327d3b38,
title = "Structures of the HIN domain:DNA complexes reveal ligand binding and activation mechanisms of the AIM2 inflammasome and IFI16 receptor",
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 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.",
keywords = "Amino Acid Sequence, Cell Line, Crystallography, X-Ray, DNA, B-Form, DNA-Binding Proteins, Humans, Immunity, Innate, Inflammasomes, Models, Molecular, Molecular Sequence Data, Nuclear Proteins, Phosphoproteins, Protein Binding, Protein Folding, Protein Structure, Tertiary, Signal Transduction",
author = "Tengchuan Jin and Andrew Perry and Jiansheng Jiang and Patrick Smith and Curry, {James A.} and Leonie Unterholzner and Zhaozhao Jiang and Gabor Horvath and Rathinam, {Vijay A.} and Johnstone, {Ricky W.} and Veit Hornung and Eicke Latz and Bowie, {Andrew G.} and Fitzgerald, {Katherine A.} and Xiao, {T. Sam}",
note = "Copyright {\textcopyright} 2012 Elsevier Inc. All rights reserved.",
year = "2012",
month = apr,
day = "20",
doi = "10.1016/j.immuni.2012.02.014",
language = "English",
volume = "36",
pages = "561--571",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "4",

}

RIS

TY - JOUR

T1 - Structures of the HIN domain:DNA complexes reveal ligand binding and activation mechanisms of the AIM2 inflammasome and IFI16 receptor

AU - Jin, Tengchuan

AU - Perry, Andrew

AU - Jiang, Jiansheng

AU - Smith, Patrick

AU - Curry, James A.

AU - Unterholzner, Leonie

AU - Jiang, Zhaozhao

AU - Horvath, Gabor

AU - Rathinam, Vijay A.

AU - Johnstone, Ricky W.

AU - Hornung, Veit

AU - Latz, Eicke

AU - Bowie, Andrew G.

AU - Fitzgerald, Katherine A.

AU - Xiao, T. Sam

N1 - Copyright © 2012 Elsevier Inc. All rights reserved.

PY - 2012/4/20

Y1 - 2012/4/20

N2 - 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.

AB - 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.

KW - Amino Acid Sequence

KW - Cell Line

KW - Crystallography, X-Ray

KW - DNA, B-Form

KW - DNA-Binding Proteins

KW - Humans

KW - Immunity, Innate

KW - Inflammasomes

KW - Models, Molecular

KW - Molecular Sequence Data

KW - Nuclear Proteins

KW - Phosphoproteins

KW - Protein Binding

KW - Protein Folding

KW - Protein Structure, Tertiary

KW - Signal Transduction

U2 - 10.1016/j.immuni.2012.02.014

DO - 10.1016/j.immuni.2012.02.014

M3 - Journal article

C2 - 22483801

VL - 36

SP - 561

EP - 571

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 4

ER -