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

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.

SUBMITTER: Jang TH

PROVIDER: S-EPMC4156391 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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

Jang Tae-Ho TH Lee Dong-Sup DS Choi Kihang K Jeong Eui Man EM Kim In-Gyu IG Kim Young Whan YW Chun Jung Nyeo JN Jeon Ju-Hong JH Park Hyun Ho HH

PloS one 20140905 9

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 end ...[more]

PMID: 25192068

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