RETRACTED: Structural basis for the coordinated regulation of transglutaminase 3 by guanine nucleotides and calcium/magnesium (Retracted Article)

被引:29
作者
Ahvazi, B
Boeshans, KM
Idler, W
Baxa, U
Steinert, PM
Rastinejad, F
机构
[1] NIAMS, Xray Crystallog Facil, NIH, Bethesda, MD 20892 USA
[2] NIAMS, Off Sci & Technol, NIH, Bethesda, MD 20892 USA
[3] NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA
[4] NIAMS, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA
[5] Univ Virginia Hlth Syst, Dept Pharmacol & Biochem & Mol Genet, Charlottesville, VA 22908 USA
关键词
D O I
10.1074/jbc.M312310200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Transglutaminase 3 (TGase 3) is a member of a family of Ca2+-dependent enzymes that catalyze covalent cross-linking reactions between proteins or peptides. TGase 3 isoform is widely expressed and is important for effective epithelial barrier formation in the assembly of the cell envelope. Among the nine TGase enzyme isoforms known in the human genome, only TGase 2 is known to bind and hydrolyze GTP to GDP; binding GTP inhibits its transamidation activity but allows it to function in signal transduction. Here we present biochemical and crystallographic evidence for the direct binding of GTP/GDP to the active TGase 3 enzyme, and we show that the TGase 3 enzyme undergoes a GTPase cycle. The crystal structures of active TGase 3 with guanosine 5% O-(thiotriphosphate) (GTPgammaS) and GDP were determined to 2.1 and 1.9 Angstrom resolution, respectively. These studies reveal for the first time the reciprocal actions of Ca2+ and GTP with respect to TGase 3 activity. GTPgammaS binding is coordinated with the replacement of a bound Ca2+ with Mg2+ and conformational rearrangements that together close a central channel to the active site. Hydrolysis of GTP to GDP results in two stable conformations, resembling both the GTP state and the nonnucleotide bound state, the latter of which allows substrate access to the active site.
引用
收藏
页码:7180 / 7192
页数:13
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