101. Inter-molecular crosslinking activity is engendered by the dimeric form of transglutaminase 2
- Author
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Seon-Hyeong Lee, Kyung-Hee Kim, Nayeon Kim, Won-Kyu Lee, Younho Lee, Soo-Youl Kim, Kyeong Sik Jin, and Minsoo Song
- Subjects
Models, Molecular ,Protein Conformation, alpha-Helical ,0301 basic medicine ,Protein Folding ,Tissue transglutaminase ,Glutamine ,Dimer ,Genetic Vectors ,Clinical Biochemistry ,Gene Expression ,Biochemistry ,Substrate Specificity ,Catalysis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Protein structure ,X-Ray Diffraction ,GTP-Binding Proteins ,Scattering, Small Angle ,Escherichia coli ,Humans ,Protein Glutamine gamma Glutamyltransferase 2 ,Protein Interaction Domains and Motifs ,Reactivity (chemistry) ,Cloning, Molecular ,chemistry.chemical_classification ,Binding Sites ,Transglutaminases ,integumentary system ,biology ,Small-angle X-ray scattering ,Lysine ,Organic Chemistry ,Temperature ,Recombinant Proteins ,Crystallography ,030104 developmental biology ,Enzyme ,Monomer ,chemistry ,030220 oncology & carcinogenesis ,Biophysics ,biology.protein ,Protein Conformation, beta-Strand ,Protein Multimerization ,Protein Binding - Abstract
Transglutaminase 2 (TGase 2) catalyzes a crosslink between protein bound-glutamine and -lysine. We proposed the mechanism of TGase 2 activation depends on conformation change from unfolded monomer to unfolded dimer. We found that TGase 2 has temperature-sensitive conformation change system at 30 °C. Small-angle X-ray scattering analysis showed that the enzyme was maintained as an unfolded monomer at temperatures below 30 °C, but changed to an unfolded dimer at over 30 °C. Mass analysis revealed that the C-terminus of TGase 2 was the critical region for dimerization. Furthermore, this conformational switch creates new biochemical reactivity that catalyzed inter-molecular crosslink at above 30 °C as an unfolded dimer of TGase 2 while catalyzed intra-molecular crosslink at below 30 °C as an unfolded monomer of TGase 2. The mechanism of TGase 2 activation depends on temperature-sensitive conformation change from unfolded monomer to unfolded dimer at over 30 °C. Furthermore, inter-molecular crosslinking activity is generated by the dimeric form of TGase 2. TGase 2 switches its conformation from a monomer to a dimer following a change in temperature, which engendered unique catalytic function of enzyme as inter-molecular crosslinking activity with calcium.
- Published
- 2016
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