title: The NMR solution structure of AIM2 PYD domain from Mus musculus reveals a distinct α2-α3 helix conformation from its human homologues.
abstract: The inflammasome is a key component of the innate immune system providing the initial defense against invading organisms. Failure of inflammasome formation is the main reason for many innate and acquired immune diseases. Cytosolic protein absent in melanoma 2 (AIM2) has been reported to play an essential role in double-stranded DNA (dsDNA) sensing and inflammasome formation in response to viruses or bacteria infection. The N-terminal pyrin domain (PYD) of AIM2 interacts with the ASC PYD domain, and then recruits downstream proteins to assemble the AIM2 inflammasome. The molecular mechanisms of PYD mediated signaling remain elusive as limited structural information on PYD family. Herein, we characterized the solution structure of mouse AIM2 PYD domain by NMR spectroscopy, and compared it with the crystal structures of its two human homologues. The comparison shows mAIM2 PYD adopts a unique α2-α3 helix conformation distinct from its human homologues, but similar to the pyrin domain of human NLRP10/PYNOD, which belongs to another family. In addition, the aggregation of mAIM2 PYD domain, with the increased salt concentration, reveals that both the charge surface and hydrophobic interaction play important roles in the self-association of mAIM2 PYD.
authors.affiliation: Beijing Nuclear Magnetic Resonance Center, Peking University, Beijing, China; College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
authors.forename: Xianhui
authors.initials: X
authors.lastname: Hou
authors.affiliation: Beijing Nuclear Magnetic Resonance Center, Peking University, Beijing, China; College of Chemistry and Molecular Engineering, Peking University, Beijing, China. Electronic address: niuxg@pku.edu.cn.
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Niu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D016415:Sequence Alignment
chemical_list: C410167:AIM2 protein, human; C540422:Aim2 protein, mouse; D004268:DNA-Binding Proteins
keywords: AIM2; Inflammasome; NMR; PYD; Self-association; Solution structure