PMID: 19153605

 

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Title : structure of the F-spondin domain of mindin , an integrin ligand and pattern recognition molecule

Abstract :

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