Crystal structure of transglutaminase 2 with GTP complex and amino acid sequence evidence of evolution of GTP binding site

Tae-Ho Jang; Dong-Sup Lee; Kihang Choi; Eui Man Jeong; In-Gyu Kim; Young Whan Kim; Jung Nyeo Chun; Ju-Hong Jeon; Hyun Ho Park

doi:10.1371/journal.pone.0107005

Crystal structure of transglutaminase 2 with GTP complex and amino acid sequence evidence of evolution of GTP binding site

PLoS One. 2014 Sep 5;9(9):e107005. doi: 10.1371/journal.pone.0107005. eCollection 2014.

Authors

Tae-Ho Jang¹, Dong-Sup Lee², Kihang Choi³, Eui Man Jeong⁴, In-Gyu Kim⁴, Young Whan Kim⁵, Jung Nyeo Chun⁶, Ju-Hong Jeon⁶, Hyun Ho Park¹

Affiliations

¹ School of Biotechnology, Yeungnam University, Gyeongsan, South Korea; Graduate School of Biochemistry, Yeungnam University, Gyeongsan, South Korea.
² Department of Physiology and Biophysics at Seoul National University College of Medicine, Seoul, South Korea.
³ Department of Chemistry, Korea University, Seoul, South Korea.
⁴ Department of Biochemistry and Molecular Biology/Aging and Apoptosis Research Center (AARC), Seoul National University College of Medicine, Seoul, South Korea.
⁵ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine, Seoul, South Korea.
⁶ Department of Physiology, Department of Biomedical Sciences, and Institute of Dermatological Science, Seoul National University College of Medicine, Seoul, South Korea.

Abstract

Transglutaminase2 (TG2) is a multi-functional protein involved in various cellular processes, including apoptosis, differentiation, wound healing, and angiogenesis. The malfunction of TG2 causes many human disease including inflammatory disease, celiac disease, neurodegenerative diseases, tissue fibrosis, and cancers. Protein cross-linking activity, which is representative of TG2, is activated by calcium ions and suppressed by GTP. Here, we elucidated the structure of TG2 in complex with its endogenous inhibitor, GTP. Our structure showed why GTP is the optimal nucleotide for interacting with and inhibiting TG2. In addition, sequence comparison provided information describing the evolutionary scenario of GTP usage for controlling the activity of TG2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Binding Sites / genetics
Crystallography, X-Ray
Evolution, Molecular
GTP-Binding Proteins / chemistry*
GTP-Binding Proteins / metabolism*
Guanosine Triphosphate / chemistry
Guanosine Triphosphate / metabolism*
Humans
Models, Molecular
Molecular Sequence Data
Protein Binding
Protein Glutamine gamma Glutamyltransferase 2
Protein Interaction Domains and Motifs / genetics*
Protein Structure, Quaternary
Protein Structure, Secondary
Sequence Homology, Amino Acid
Transglutaminases / chemistry*
Transglutaminases / metabolism*

Substances

Guanosine Triphosphate
Protein Glutamine gamma Glutamyltransferase 2
Transglutaminases
GTP-Binding Proteins

Grants and funding

This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A100190). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.