GTP is required to stabilize and display transamidation activity of transglutaminase 2.
Transglutaminase 2 (TGase 2) is a bifunctional enzyme that catalyzes calcium-dependent transamidation and GTP binding/hydrolysis. The transamidation activity is proposed to be associated with several neurodegenerative disorders such as Alzheimer's and Hungtinton's disease. However, the regulation mechanism by which TGase 2 causes neurodegeneration is unknown. In this study, we show that two activities of TGase 2 have a differential stability; transamidation activity is less stable than GTP hydrolytic activity, and that GTP was required to stabilize and to display transamidation activity. Moreover, GTP binding-defective mutant of TGase 2 did not show any transamidation activity in transfection experiments. These results indicate that GTP binding is crucial for transamidation activity of TGase 2, suggesting that protein cross-linking by TGase 2 might be associated with G-protein coupled receptor signaling system. Thus, our data could contribute to understand the regulation of TGase 2 activity and TGase 2-associated pathogenesis.
Jeon
Ju-Hong
JH
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, 28 Yongon Dong, Chongno Gu, Republic of Korea.
Cho
Sung-Yup
SY
Kim
Chai-Wan
CW
Shin
Dong-Myung
DM
Kweon
Joon-Chul
JC
Choi
Kyung-Ho
KH
Park
Sang-Chul
SC
Kim
In-Gyu
IG
D016475:3T3 Cells; D000818:Animals; D004912:Erythrocytes / Q000201:enzymology; D019204:GTP-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology; D006160:Guanosine Triphosphate / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006868:Hydrolysis; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009474:Neurons / Q000201:enzymology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D013997:Time Factors; D014162:Transfection; D011503:Transglutaminases / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology
D006160:Guanosine Triphosphate; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins