 |
PDBsum entry 4l5t
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Immune system
|
PDB id
|
|
|
|
4l5t
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
PDB id:
|
|
|
|
| Name: |
|
Immune system
|
|
|
Title:
|
|
Crystal structure of the tetrameric p202 hin2
|
|
Structure:
|
|
Interferon-activable protein 202. Chain: a, b, c, d. Fragment: p202 hin2, unp residues 244-445. Synonym: ifi-202, interferon-inducible protein p202, lupus susceptibility protein p202. Engineered: yes
|
|
Source:
|
|
Mus musculus. Mouse. Organism_taxid: 10090. Strain: czech ii. Gene: ifi202, ifi202a, ifi202b. Expressed in: escherichia coli. Expression_system_taxid: 469008.
|
|
Resolution:
|
|
|
3.41Å
|
R-factor:
|
0.212
|
R-free:
|
0.268
|
|
|
Authors:
|
|
Q.Yin,Y.Tian,H.Wu
|
|
Key ref:
|
|
Q.Yin
et al.
(2013).
Molecular mechanism for p202-mediated specific inhibition of AIM2 inflammasome activation.
Cell Rep,
4,
327-339.
PubMed id:
DOI:
|
|
|
Date:
|
|
|
11-Jun-13
|
Release date:
|
31-Jul-13
|
|
|
|
|
|
|
PROCHECK
|
|
|
|
|
|
Headers
|
|
|
|
References
|
|
|
|
|
|
|
|
Q9R002
(IFI2_MOUSE) -
Interferon-activable protein 202 from Mus musculus
|
|
|
|
Seq:
Struc:
|
|
|
|
445 a.a.
180 a.a.*
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Key: |
 |
PfamA domain |
|
|
 |
Secondary structure |
|
 |
CATH domain |
|
|
*
PDB and UniProt seqs differ
at 3 residue positions (black
crosses)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
DOI no:
|
Cell Rep
4:327-339
(2013)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Molecular mechanism for p202-mediated specific inhibition of AIM2 inflammasome activation.
|
|
Q.Yin,
D.P.Sester,
Y.Tian,
Y.S.Hsiao,
A.Lu,
J.A.Cridland,
V.Sagulenko,
S.J.Thygesen,
D.Choubey,
V.Hornung,
T.Walz,
K.J.Stacey,
H.Wu.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Mouse p202 containing two hemopoietic expression, interferon inducibility,
nuclear localization (HIN) domains antagonizes AIM2 inflammasome signaling and
potentially modifies lupus susceptibility. We found that only HIN1 of p202 binds
double-stranded DNA (dsDNA), while HIN2 forms a homotetramer. Crystal structures
of HIN1 revealed that dsDNA is bound on face opposite the site used in AIM2 and
IFI16. The structure of HIN2 revealed a dimer of dimers, the face analogous to
the HIN1 dsDNA binding site being a dimerization interface. Electron microscopy
imaging showed that HIN1 is flexibly linked to HIN2 in p202, and tetramerization
provided enhanced avidity for dsDNA. Surprisingly, HIN2 of p202 interacts with
the AIM HIN domain. We propose that this results in a spatial separation of the
AIM2 pyrin domains, and indeed p202 prevented the dsDNA-dependent clustering of
apoptosis-associated speck-like protein containing caspase recruitment domain
(ASC) and AIM2 inflammasome activation. We hypothesize that while p202 was
evolutionarily selected to limit AIM2-mediated inflammation in some mouse
strains, the same mechanism contributes to increased interferon production and
lupus susceptibility.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Links
