Mapping the minimum domain of the fibronectin binding site on transglutaminase 2 (TG2) and its importance in mediating signaling, adhesion, and migration in TG2-expressing cells
Type
ArticleAuthors
Soluri, Maria FeliciaBoccafoschi, Francesca
Cotella, Diego
Moro, Laura
Forestieri, Gabriela
Autiero, Ida
Cavallo, Luigi

Oliva, Romina
Griffin, Martin
Wang, Zhuo
Santoro, Claudio
Sblattero, Daniele
KAUST Department
Chemical Science ProgramComputational Bioscience Research Center (CBRC)
Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
KAUST Catalysis Center (KCC)
Physical Science and Engineering (PSE) Division
Date
2018-10-04Permanent link to this record
http://hdl.handle.net/10754/630578
Metadata
Show full item recordAbstract
The interaction between the enzyme transglutaminase 2 (TG2) and fibronectin (FN) is involved in the cell-matrix interactions that regulate cell signaling, adhesion, and migration and play central roles in pathologic conditions, particularly fibrosis and cancer. A precise definition of the exact interaction domains on both proteins could provide a tool to design novel molecules with potential therapeutic applications. Although specific residues involved in the interaction within TG2 have been analyzed, little is known regarding the TG2 binding site on FN. This site has been mapped to a large internal 45-kDa protein fragment coincident with the gelatin binding domain (GBD). With the goal of defining the minimal FN interacting domain for TG2, we produced several expression constructs encoding different portions or modules of the GBD and tested their binding and functional properties. The results demonstrate that the I8 module is necessary and sufficient for TG2-binding in vitro, but does not have functional effects on TG2-expressing cells. Modules I7 and I9 increase the strength of the binding and are required for cell adhesion. A 15-kDa fragment encompassing modules I7-9 behaves as the whole 45-kDa GBD and mediates signaling, adhesion, spreading, and migration of TG2+ cells. This study provides new insights into the mechanism for TG2 binding to FN.-Soluri, M. F., Boccafoschi, F., Cotella, D., Moro, L., Forestieri, G., Autiero, I., Cavallo, L., Oliva, R., Griffin, M., Wang, Z., Santoro, C., Sblattero, D. Mapping the minimum domain of the fibronectin binding site on transglutaminase 2 (TG2) and its importance in mediating signaling, adhesion, and migration in TG2-expressing cells.Citation
Soluri MF, Boccafoschi F, Cotella D, Moro L, Forestieri G, et al. (2018) Mapping the minimum domain of the fibronectin binding site on transglutaminase 2 (TG2) and its importance in mediating signaling, adhesion, and migration in TG2-expressing cells. The FASEB Journal: fj.201800054RRR. Available: http://dx.doi.org/10.1096/fj.201800054rrr.Publisher
FASEBJournal
The FASEB JournalAdditional Links
https://www.fasebj.org/doi/10.1096/fj.201800054RRRae974a485f413a2113503eed53cd6c53
10.1096/fj.201800054rrr