title: Crystal structure of human POP1 and its distinct structural feature for PYD domain.
abstract: 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.
authors.affiliation: School of Biotechnology and Graduate School of Biochemistry at Yeungnam University, Gyeongsan 712-749, South Korea.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: School of Biotechnology and Graduate School of Biochemistry at Yeungnam University, Gyeongsan 712-749, South Korea.
authors.forename: Chang Min
authors.initials: CM
authors.lastname: Kim
authors.affiliation: School of Biotechnology and Graduate School of Biochemistry at Yeungnam University, Gyeongsan 712-749, South Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Seo
authors.affiliation: School of Biotechnology and Graduate School of Biochemistry at Yeungnam University, Gyeongsan 712-749, South Korea.
authors.forename: Eijaz Ahmed
authors.initials: EA
authors.lastname: Bhat
authors.affiliation: School of Biotechnology and Graduate School of Biochemistry at Yeungnam University, Gyeongsan 712-749, South Korea.
authors.forename: Tae-Ho
authors.initials: TH
authors.lastname: Jang
authors.affiliation: Division of Polar Life Sciences, Korea Polar Research Institute, Incheon 406-840, Republic of Korea; Department of Polar Sciences, Korea University of Science and Technology, Incheon 406-840, Republic of Korea.
authors.forename: Jun Hyuck
authors.initials: JH
authors.lastname: Lee
authors.affiliation: School of Biotechnology and Graduate School of Biochemistry at Yeungnam University, Gyeongsan 712-749, South Korea. Electronic address: hyunho@ynu.ac.kr.
authors.forename: Hyun Ho
authors.initials: HH
authors.lastname: Park
mesh_terms: D000595:Amino Acid Sequence; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry*; D020170:Caspase 1 / Q000737:chemistry; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012261:Ribonucleoproteins / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid
chemical_list: D051017:Apoptosis Regulatory Proteins; C490350:POP1 protein, human; D012261:Ribonucleoproteins; D020170:Caspase 1
keywords: Crystal structure; Inflammasome; Inflammation; Innate immunity; POP1; PYD domain