3D34

Structure of the F-spondin domain of mindin

3D34 の概要

• エントリーDOI: 10.2210/pdb3d34/pdb
• 分子名称: Spondin-2, NICKEL (II) ION, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: f-spondin domain of mindin, cell adhesion, extracellular matrix, immune response, polymorphism, secreted, immune system
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Secreted, extracellular space, extracellular matrix : Q9BUD6
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 49771.41

構造登録者

Li, Y.,Mariuzza, R.A. (登録日: 2008-05-09, 公開日: 2009-02-17, 最終更新日: 2024-10-30)

主引用文献

Li, Y.,Cao, C.,Jia, W.,Yu, L.,Mo, M.,Wang, Q.,Huang, Y.,Lim, J.M.,Ishihara, M.,Wells, L.,Azadi, P.,Robinson, H.,He, Y.W.,Zhang, L.,Mariuzza, R.A.
Structure of the F-spondin domain of mindin, an integrin ligand and pattern recognition molecule.
Embo J., 28:286-297, 2009

PubMed Abstract: 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.

PubMed: 19153605
DOI: 10.1038/emboj.2008.288

実験手法

X-RAY DIFFRACTION (1.8 Å)