Structure of the F-spondin domain of mindin, an integrin ligand and pattern recognition molecule.

نویسندگان

  • Yili Li
  • Chunzhang Cao
  • Wei Jia
  • Lily Yu
  • Min Mo
  • Qian Wang
  • Yuping Huang
  • Jae-Min Lim
  • Mayumi Ishihara
  • Lance Wells
  • Parastoo Azadi
  • Howard Robinson
  • You-Wen He
  • Li Zhang
  • Roy A Mariuzza
چکیده

Mindin (spondin-2) is an extracellular matrix protein of unknown structure that is required for efficient T-cell priming by dendritic cells. Additionally, mindin functions as a pattern recognition molecule for initiating innate immune responses. These dual functions are mediated by interactions with integrins and microbial pathogens, respectively. Mindin comprises an N-terminal F-spondin (FS) domain and C-terminal thrombospondin type 1 repeat (TSR). We determined the structure of the FS domain at 1.8-A resolution. The structure revealed an eight-stranded antiparallel beta-sandwich motif resembling that of membrane-targeting C2 domains, including a bound calcium ion. We demonstrated that the FS domain mediates integrin binding and identified the binding site by mutagenesis. The mindin FS domain therefore represents a new integrin ligand. We further showed that mindin recognizes lipopolysaccharide (LPS) through its TSR domain, and obtained evidence that C-mannosylation of the TSR influences LPS binding. Through these dual interactions, the FS and TSR domains of mindin promote activation of both adaptive and innate immune responses.

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عنوان ژورنال:
  • The EMBO journal

دوره 28 3  شماره 

صفحات  -

تاریخ انتشار 2009