Structure of the F-spondin domain of mindin, an integrin ligand and pattern recognition molecule.
نویسندگان
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.
منابع مشابه
Role of Mindin in Diabetic Nephropathy
A number of studies have shown that proinflammatory cytokines have important roles in determining the development of microvascular diabetic complications, including nephropathy. Inflammatory biomarkers should be useful for diagnosis or monitoring of diabetic nephropathy. Mindin (spondin 2) is a member of the mindin-/F-spondin family of secreted extracellular matrix (ECM) proteins. Recent studie...
متن کاملThe extracellular matrix protein mindin serves as an integrin ligand and is critical for inflammatory cell recruitment.
Leukocyte recruitment to inflammation sites depends on interactions between integrins and extracellular matrix (ECM). In this report we show that mice lacking the ECM protein mindin exhibit severely impaired recruitment of neutrophils and macrophages in 4 different inflammation models. Furthermore, neutrophils directly bind to immobilized mindin, and mindin matrix mediates neutrophil migration ...
متن کاملMolecular docking and in silico ADME prediction of Ticagrelor as an antagonist of the P2Y12 receptor
The purpose of the present research work is prediction of electronic and physico-chemical properties of the novel medicinal compound Ticagrelor (AZD6140) using density functional theory (DFT) method. Firstly, its molecular structure was optimized at B3LYP/6-311++G(d,p) basis set of theory at room temperature. The global reactivity indices used to study the reactivity and stability of the title ...
متن کاملBinding of F-spondin to amyloid- precursor protein: A candidate amyloid- precursor protein ligand that modulates amyloid- precursor protein cleavage
Amyloidprecursor protein (APP), a type I membrane protein, is physiologically processed by or -secretases that cleave APP N-terminal to the transmembrane region. Extracellular -cleavage of APP generates a large secreted N-terminal fragment, and a smaller cellular C-terminal fragment. Subsequent -secretase cleavage in the transmembrane region of the C-terminal fragment induces secretion of small...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The EMBO journal
دوره 28 3 شماره
صفحات -
تاریخ انتشار 2009