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Amino Acids. 2017 Mar;49(3):461-471. doi: 10.1007/s00726-016-2293-1. Epub 2016 Jul 9.

Inter-molecular crosslinking activity is engendered by the dimeric form of transglutaminase 2.

Author information

1
Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, 10408, Republic of Korea.
2
Department of Chemistry, College of Science, Dongguk University, Seoul, 04620, Republic of Korea.
3
Institute of Life Science and Natural Resources, Korea University, Seoul, 02841, Republic of Korea.
4
Pohang Accelerator Laboratory, Pohang University of Science and Technology, 80 Jigokro-127-beongil, Pohang, 37673, Republic of Korea.
5
Omics Core Laboratory, Research Institute, National Cancer Center, Goyang, 10408, Republic of Korea.
6
New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, 80 Cheombok-ro, Dong-gu, Daegu, 41061, Republic of Korea.
7
Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, 10408, Republic of Korea. kimsooyoul@gmail.com.

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.

KEYWORDS:

Dimerization; Protein structures; SAXS; Transglutaminase 2

PMID:
27394142
DOI:
10.1007/s00726-016-2293-1
[Indexed for MEDLINE]

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