The role of calcium ions in the regulation of tissue transglutaminase is investigated by experimental approaches and computer modeling. A three-dimensional model of the transglutaminase is computed by homology building on crystallized human factor XIII and is used to interpret structural and functional results. The molecule is a prolate ellipsoid (6.2 x 4.2 x 11 nm) and comprises four domains, assembled pairwise into N-terminal and C-terminal regions. The active site is hidden in a cleft between these regions and is inaccessible to macromolecular substrates in the calcium-for form, Protein dynamics simulation indicates that these regions move apart upon addition of calcium ions, revealing the active site for catalysis. The protein dimensions are consistent with results obtained with small-angle neutron and X-rap scattering. The gyration radius of the protein (3 nm) increases in the presence of calcium ions (3.9 nm), but it is virtually unaffected in the presence of GTP, suggesting that only calcium ions can promote major structural changes in the native protein. Proteolysis of an exposed loop connecting the N-terminal and C-terminal regions is linearly correlated with enzyme inactivation and prevents the calcium-induced conformational changes.

The structural basis for the regulation of tissue transglutaminase by calcium ions / Casadio, R.; Polverini, Eugenia; Mariani, P.; Spinozzi, F.; Carsughi, F.; Fontana, A.; POLVERINO DE LAURETO, P.; Matteucci, G.; Bergamini, C. M.. - In: EUROPEAN JOURNAL OF BIOCHEMISTRY. - ISSN 0014-2956. - 262:3(1999), pp. 672-679. [10.1046/j.1432-1327.1999.00437.x]

The structural basis for the regulation of tissue transglutaminase by calcium ions

POLVERINI, Eugenia;
1999-01-01

Abstract

The role of calcium ions in the regulation of tissue transglutaminase is investigated by experimental approaches and computer modeling. A three-dimensional model of the transglutaminase is computed by homology building on crystallized human factor XIII and is used to interpret structural and functional results. The molecule is a prolate ellipsoid (6.2 x 4.2 x 11 nm) and comprises four domains, assembled pairwise into N-terminal and C-terminal regions. The active site is hidden in a cleft between these regions and is inaccessible to macromolecular substrates in the calcium-for form, Protein dynamics simulation indicates that these regions move apart upon addition of calcium ions, revealing the active site for catalysis. The protein dimensions are consistent with results obtained with small-angle neutron and X-rap scattering. The gyration radius of the protein (3 nm) increases in the presence of calcium ions (3.9 nm), but it is virtually unaffected in the presence of GTP, suggesting that only calcium ions can promote major structural changes in the native protein. Proteolysis of an exposed loop connecting the N-terminal and C-terminal regions is linearly correlated with enzyme inactivation and prevents the calcium-induced conformational changes.
1999
The structural basis for the regulation of tissue transglutaminase by calcium ions / Casadio, R.; Polverini, Eugenia; Mariani, P.; Spinozzi, F.; Carsughi, F.; Fontana, A.; POLVERINO DE LAURETO, P.; Matteucci, G.; Bergamini, C. M.. - In: EUROPEAN JOURNAL OF BIOCHEMISTRY. - ISSN 0014-2956. - 262:3(1999), pp. 672-679. [10.1046/j.1432-1327.1999.00437.x]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/1458864
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 103
  • ???jsp.display-item.citation.isi??? 95
social impact