title: Inter-molecular crosslinking activity is engendered by the dimeric form of transglutaminase 2.
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.
authors.affiliation: Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, 10408, Republic of Korea.|Department of Chemistry, College of Science, Dongguk University, Seoul, 04620, Republic of Korea.
authors.forename: Nayeon
authors.initials: N
authors.lastname: Kim
authors.affiliation: Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, 10408, Republic of Korea.|Institute of Life Science and Natural Resources, Korea University, Seoul, 02841, Republic of Korea.
authors.forename: Won-Kyu
authors.initials: WK
authors.lastname: Lee
authors.affiliation: Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, 10408, Republic of Korea.
authors.forename: Seon-Hyeong
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Pohang Accelerator Laboratory, Pohang University of Science and Technology, 80 Jigokro-127-beongil, Pohang, 37673, Republic of Korea.
authors.forename: Kyeong Sik
authors.initials: KS
authors.lastname: Jin
authors.affiliation: Omics Core Laboratory, Research Institute, National Cancer Center, Goyang, 10408, Republic of Korea.
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Kim
authors.affiliation: New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, 80 Cheombok-ro, Dong-gu, Daegu, 41061, Republic of Korea.
authors.forename: Younho
authors.initials: Y
authors.lastname: Lee
authors.affiliation: New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, 80 Cheombok-ro, Dong-gu, Daegu, 41061, Republic of Korea.
authors.forename: Minsoo
authors.initials: M
authors.lastname: Song
authors.affiliation: Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, 10408, Republic of Korea. kimsooyoul@gmail.com.
authors.forename: Soo-Youl
authors.initials: SY
authors.lastname: Kim
mesh_terms: D001665:Binding Sites; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D005973:Glutamine / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D017510:Protein Folding; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D053838:Scattering, Small Angle; D013379:Substrate Specificity; D013696:Temperature; D011503:Transglutaminases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014961:X-Ray Diffraction
chemical_list: D011994:Recombinant Proteins; D005973:Glutamine; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D008239:Lysine
keywords: Dimerization; Protein structures; SAXS; Transglutaminase 2