Crystal structure of human POP1 and its distinct structural feature for PYD domain

Inflammatory caspases, such as caspase-1, which is critical for the innate immune response, are activated upon the formation of a molecular complex called the inflammasome. The inflammasome is composed of three proteins, the Nod-like receptor (NLRP, NLRC or AIM2), apoptosis associated speck-loke pro...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2015-05, Vol.460 (4), p.957-963
Main Authors: Choi, Jae Young, Kim, Chang Min, Seo, Eun Kyung, Bhat, Eijaz Ahmed, Jang, Tae-ho, Lee, Jun Hyuck, Park, Hyun Ho
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Apoptosis Regulatory Proteins - chemistry
Caspase 1 - chemistry
Crystal structure
Crystallography, X-Ray
Humans
Inflammasome
Inflammation
Innate immunity
Models, Molecular
Molecular Sequence Data
POP1
Protein Conformation
PYD domain
Ribonucleoproteins - chemistry
Sequence Homology, Amino Acid
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Summary:Inflammatory caspases, such as caspase-1, which is critical for the innate immune response, are activated upon the formation of a molecular complex called the inflammasome. The inflammasome is composed of three proteins, the Nod-like receptor (NLRP, NLRC or AIM2), apoptosis associated speck-loke protein containing a caspase-recruitment domain (ASC), and caspase-1. ASC is an adaptor molecule that contains an N-terminal PYD domain and a C-terminal CARD domain for interaction with other proteins. Upon activation, the N-terminal PYD of ASC homotypically interacts with the PYD domain of the Nod-like receptor, while its C-terminal CARD homotypically interacts with the CARD domain of caspase-1. PYD only protein 1 (POP1) negatively regulates inflammatory response by blocking the formation of the inflammasome. POP1 directly binds to ASC via a PYD:PYD interaction, thereby preventing ASC recruitment to Nod-like receptor NLRPs. POP1-mediated regulation of inflammation is of great biological importance. Here, we report the crystal structure of human POP1 and speculate about the inhibitory mechanism of POP1-mediated inflammasome formation based on the current structure. •We solved the crystal structure of POP1 protein.•We found distinct structural difference between death domain superfamily.•We speculate the inhibitory mechanism of POP1-mediated inflammasome formation based on the structure.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2015.03.134