The structural basis for the regulation of tissue transglutaminase by calcium ions
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 functio...
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| Veröffentlicht in: | European journal of biochemistry 1999-06, Vol.262 (3), p.672-679 |
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| container_title | European journal of biochemistry |
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| creator | Casadio, Rita Polverini, Eugenia Mariani, Paolo Spinozzi, Francesco Carsughi, Flavio Fontana, Angelo de Laureto, Patrizia Polverino Matteucci, Gabriella Bergamini, Carlo M. |
| description | 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 × 4.2 × 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‐free 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‐ray 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. |
| doi_str_mv | 10.1046/j.1432-1327.1999.00437.x |
| format | Article |
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The protein dimensions are consistent with results obtained with small‐angle neutron and X‐ray 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.</description><identifier>ISSN: 0014-2956</identifier><identifier>EISSN: 1432-1033</identifier><identifier>DOI: 10.1046/j.1432-1327.1999.00437.x</identifier><identifier>PMID: 10411627</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Amino Acid Sequence ; Calcium - physiology ; calcium conformational changes ; Computer Simulation ; Endopeptidases - metabolism ; Factor XIII - chemistry ; GTP Phosphohydrolases - chemistry ; GTP Phosphohydrolases - metabolism ; GTP-Binding Proteins ; Humans ; Hydrolysis ; ligand effect ; Models, Molecular ; Molecular Sequence Data ; Protein Conformation ; Protein Denaturation ; protein modeling ; Scattering, Radiation ; small‐angle scattering ; transglutaminase ; Transglutaminases - chemistry ; Transglutaminases - metabolism ; X-Rays</subject><ispartof>European journal of biochemistry, 1999-06, Vol.262 (3), p.672-679</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4817-51afdc97c0a343cff032216e16c997ec7cd140fe88c9a370b8879cfea1fc01b03</citedby><cites>FETCH-LOGICAL-c4817-51afdc97c0a343cff032216e16c997ec7cd140fe88c9a370b8879cfea1fc01b03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1432-1327.1999.00437.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1432-1327.1999.00437.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10411627$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Casadio, Rita</creatorcontrib><creatorcontrib>Polverini, Eugenia</creatorcontrib><creatorcontrib>Mariani, Paolo</creatorcontrib><creatorcontrib>Spinozzi, Francesco</creatorcontrib><creatorcontrib>Carsughi, Flavio</creatorcontrib><creatorcontrib>Fontana, Angelo</creatorcontrib><creatorcontrib>de Laureto, Patrizia Polverino</creatorcontrib><creatorcontrib>Matteucci, Gabriella</creatorcontrib><creatorcontrib>Bergamini, Carlo M.</creatorcontrib><title>The structural basis for the regulation of tissue transglutaminase by calcium ions</title><title>European journal of biochemistry</title><addtitle>Eur J Biochem</addtitle><description>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 × 4.2 × 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‐free 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‐ray 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.</description><subject>Amino Acid Sequence</subject><subject>Calcium - physiology</subject><subject>calcium conformational changes</subject><subject>Computer Simulation</subject><subject>Endopeptidases - metabolism</subject><subject>Factor XIII - chemistry</subject><subject>GTP Phosphohydrolases - chemistry</subject><subject>GTP Phosphohydrolases - metabolism</subject><subject>GTP-Binding Proteins</subject><subject>Humans</subject><subject>Hydrolysis</subject><subject>ligand effect</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Protein Conformation</subject><subject>Protein Denaturation</subject><subject>protein modeling</subject><subject>Scattering, Radiation</subject><subject>small‐angle scattering</subject><subject>transglutaminase</subject><subject>Transglutaminases - chemistry</subject><subject>Transglutaminases - metabolism</subject><subject>X-Rays</subject><issn>0014-2956</issn><issn>1432-1033</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkLFOwzAQhi0EoqXwCsgTW8I5Tu14YICqBaRKSFBmy3Htksppih2L9u1JCAMj05103_-f9CGECaQEcna7TUlOs4TQjKdECJEC5JSnhxM0Hg5A6SkaA5A8ycSUjdBFCFsAYILxczTqSghhGR-j19WHwaH1UbfRK4dLFaqAbeNx2x282USn2qrZ4cbitgohGtx6tQsbF1tVVzsVDC6PWCunq1jjjgyX6MwqF8zV75yg98V8NXtKli-Pz7P7ZaLzgvBkSpRda8E1KJpTbS3QLCPMEKaF4EZzvSY5WFMUWijKoSwKLrQ1ilgNpAQ6QTdD7943n9GEVtZV0MY5tTNNDJKJQnA-zTqwGEDtmxC8sXLvq1r5oyQge59yK3ttsvcpe5_yx6c8dNHr3x-xrM36T3AQ2AF3A_BVOXP8d7FczB_euo1-A_iIhVE</recordid><startdate>199906</startdate><enddate>199906</enddate><creator>Casadio, Rita</creator><creator>Polverini, Eugenia</creator><creator>Mariani, Paolo</creator><creator>Spinozzi, Francesco</creator><creator>Carsughi, Flavio</creator><creator>Fontana, Angelo</creator><creator>de Laureto, Patrizia Polverino</creator><creator>Matteucci, Gabriella</creator><creator>Bergamini, Carlo M.</creator><general>Blackwell Science Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>199906</creationdate><title>The structural basis for the regulation of tissue transglutaminase by calcium ions</title><author>Casadio, Rita ; Polverini, Eugenia ; Mariani, Paolo ; Spinozzi, Francesco ; Carsughi, Flavio ; Fontana, Angelo ; de Laureto, Patrizia Polverino ; Matteucci, Gabriella ; Bergamini, Carlo M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4817-51afdc97c0a343cff032216e16c997ec7cd140fe88c9a370b8879cfea1fc01b03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Amino Acid Sequence</topic><topic>Calcium - physiology</topic><topic>calcium conformational changes</topic><topic>Computer Simulation</topic><topic>Endopeptidases - metabolism</topic><topic>Factor XIII - chemistry</topic><topic>GTP Phosphohydrolases - chemistry</topic><topic>GTP Phosphohydrolases - metabolism</topic><topic>GTP-Binding Proteins</topic><topic>Humans</topic><topic>Hydrolysis</topic><topic>ligand effect</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>Protein Conformation</topic><topic>Protein Denaturation</topic><topic>protein modeling</topic><topic>Scattering, Radiation</topic><topic>small‐angle scattering</topic><topic>transglutaminase</topic><topic>Transglutaminases - chemistry</topic><topic>Transglutaminases - metabolism</topic><topic>X-Rays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Casadio, Rita</creatorcontrib><creatorcontrib>Polverini, Eugenia</creatorcontrib><creatorcontrib>Mariani, Paolo</creatorcontrib><creatorcontrib>Spinozzi, Francesco</creatorcontrib><creatorcontrib>Carsughi, Flavio</creatorcontrib><creatorcontrib>Fontana, Angelo</creatorcontrib><creatorcontrib>de Laureto, Patrizia Polverino</creatorcontrib><creatorcontrib>Matteucci, Gabriella</creatorcontrib><creatorcontrib>Bergamini, Carlo M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Casadio, Rita</au><au>Polverini, Eugenia</au><au>Mariani, Paolo</au><au>Spinozzi, Francesco</au><au>Carsughi, Flavio</au><au>Fontana, Angelo</au><au>de Laureto, Patrizia Polverino</au><au>Matteucci, Gabriella</au><au>Bergamini, Carlo M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The structural basis for the regulation of tissue transglutaminase by calcium ions</atitle><jtitle>European journal of biochemistry</jtitle><addtitle>Eur J Biochem</addtitle><date>1999-06</date><risdate>1999</risdate><volume>262</volume><issue>3</issue><spage>672</spage><epage>679</epage><pages>672-679</pages><issn>0014-2956</issn><eissn>1432-1033</eissn><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 × 4.2 × 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‐free 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‐ray 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.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>10411627</pmid><doi>10.1046/j.1432-1327.1999.00437.x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| language | eng |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Alma/SFX Local Collection |
| subjects | Amino Acid Sequence Calcium - physiology calcium conformational changes Computer Simulation Endopeptidases - metabolism Factor XIII - chemistry GTP Phosphohydrolases - chemistry GTP Phosphohydrolases - metabolism GTP-Binding Proteins Humans Hydrolysis ligand effect Models, Molecular Molecular Sequence Data Protein Conformation Protein Denaturation protein modeling Scattering, Radiation small‐angle scattering transglutaminase Transglutaminases - chemistry Transglutaminases - metabolism X-Rays |
| title | The structural basis for the regulation of tissue transglutaminase by calcium ions |
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