Structure of the Chlamydia Protein CADD Reveals a Redox Enzyme That Modulates Host Cell Apoptosis
The Chlamydia protein CADD ( C hlamydia protein a ssociating with d eath d omains) has been implicated in the modulation of host cell apoptosis via binding to the death domains of tumor necrosis factor family receptors. Transfection of CADD into mammalian cells induces apoptosis. Here we present the...
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| Veröffentlicht in: | The Journal of biological chemistry 2004-07, Vol.279 (28), p.29320-29324 |
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| container_end_page | 29324 |
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| container_issue | 28 |
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| container_title | The Journal of biological chemistry |
| container_volume | 279 |
| creator | Schwarzenbacher, Robert Stenner-Liewen, Frank Liewen, Heike Robinson, Howard Yuan, Hua Bossy-Wetzel, Ella Reed, John C Liddington, Robert C |
| description | The Chlamydia protein CADD ( C hlamydia protein a ssociating with d eath d omains) has been implicated in the modulation of host cell apoptosis via binding to the death domains of tumor necrosis factor
family receptors. Transfection of CADD into mammalian cells induces apoptosis. Here we present the CADD crystal structure,
which reveals a dimer of seven-helix bundles. Each bundle contains a di-iron center adjacent to an internal cavity, forming
an active site similar to that of methane mono-oxygenase hydrolase. We further show that CADD mutants lacking critical metal-coordinating
residues are substantially less effective in inducing apoptosis but retain their ability to bind to death domains. We conclude
that CADD is a novel redox protein toxin unique to Chlamydia species and propose that both its redox activity and death domain binding ability are required for its biological activity. |
| doi_str_mv | 10.1074/jbc.M401268200 |
| format | Article |
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family receptors. Transfection of CADD into mammalian cells induces apoptosis. Here we present the CADD crystal structure,
which reveals a dimer of seven-helix bundles. Each bundle contains a di-iron center adjacent to an internal cavity, forming
an active site similar to that of methane mono-oxygenase hydrolase. We further show that CADD mutants lacking critical metal-coordinating
residues are substantially less effective in inducing apoptosis but retain their ability to bind to death domains. We conclude
that CADD is a novel redox protein toxin unique to Chlamydia species and propose that both its redox activity and death domain binding ability are required for its biological activity.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M401268200</identifier><identifier>PMID: 15087448</identifier><language>eng</language><publisher>United States: American Society for Biochemistry and Molecular Biology</publisher><subject>Amino Acid Sequence ; Apoptosis - physiology ; Bacterial Proteins - chemistry ; Bacterial Proteins - genetics ; Bacterial Proteins - metabolism ; Binding Sites ; Chlamydia ; Chlamydia trachomatis - enzymology ; Chlamydia trachomatis - physiology ; Crystallography, X-Ray ; Humans ; Iron - metabolism ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Oxidation-Reduction ; Protein Structure, Tertiary ; Sequence Alignment</subject><ispartof>The Journal of biological chemistry, 2004-07, Vol.279 (28), p.29320-29324</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-4b783f6fd3a9302787863c0e60466221aba89279fbceb1a4b64e7363709330f23</citedby><cites>FETCH-LOGICAL-c391t-4b783f6fd3a9302787863c0e60466221aba89279fbceb1a4b64e7363709330f23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15087448$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schwarzenbacher, Robert</creatorcontrib><creatorcontrib>Stenner-Liewen, Frank</creatorcontrib><creatorcontrib>Liewen, Heike</creatorcontrib><creatorcontrib>Robinson, Howard</creatorcontrib><creatorcontrib>Yuan, Hua</creatorcontrib><creatorcontrib>Bossy-Wetzel, Ella</creatorcontrib><creatorcontrib>Reed, John C</creatorcontrib><creatorcontrib>Liddington, Robert C</creatorcontrib><title>Structure of the Chlamydia Protein CADD Reveals a Redox Enzyme That Modulates Host Cell Apoptosis</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>The Chlamydia protein CADD ( C hlamydia protein a ssociating with d eath d omains) has been implicated in the modulation of host cell apoptosis via binding to the death domains of tumor necrosis factor
family receptors. Transfection of CADD into mammalian cells induces apoptosis. Here we present the CADD crystal structure,
which reveals a dimer of seven-helix bundles. Each bundle contains a di-iron center adjacent to an internal cavity, forming
an active site similar to that of methane mono-oxygenase hydrolase. We further show that CADD mutants lacking critical metal-coordinating
residues are substantially less effective in inducing apoptosis but retain their ability to bind to death domains. We conclude
that CADD is a novel redox protein toxin unique to Chlamydia species and propose that both its redox activity and death domain binding ability are required for its biological activity.</description><subject>Amino Acid Sequence</subject><subject>Apoptosis - physiology</subject><subject>Bacterial Proteins - chemistry</subject><subject>Bacterial Proteins - genetics</subject><subject>Bacterial Proteins - metabolism</subject><subject>Binding Sites</subject><subject>Chlamydia</subject><subject>Chlamydia trachomatis - enzymology</subject><subject>Chlamydia trachomatis - physiology</subject><subject>Crystallography, X-Ray</subject><subject>Humans</subject><subject>Iron - metabolism</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis, Site-Directed</subject><subject>Oxidation-Reduction</subject><subject>Protein Structure, Tertiary</subject><subject>Sequence Alignment</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1r3DAQhkVoSTZprz0WHUpu3o4-1pKOi_MJCS1tCr0J2R7XDvZqK8lptr8-CruQucwcnvdleAj5xGDJQMmvj3WzvJfAeKk5wBFZMNCiECv2-x1ZAHBWGL7SJ-Q0xkfIIw07JidsBVpJqRfE_UxhbtIckPqOph5p1Y9u2rWDo9-DTzhsaLW-uKA_8AndGKnLV-uf6eXm_25C-tC7RO99O48uYaQ3PiZa4TjS9dZvk49D_EDedzmIHw_7jPy6unyoboq7b9e31fquaIRhqZC10qIru1Y4I4ArrXQpGsASZFlyzlzttOHKdHWDNXOyLiUqUQoFRgjouDgj5_vebfB_Z4zJTkNs8itug36OlinNhTIyg8s92AQfY8DObsMwubCzDOyrVJul2jepOfD50DzXE7Zv-MFiBr7sgX740_8bAtp68E2Pk80PW64tN4KDeAEDkH0F</recordid><startdate>20040709</startdate><enddate>20040709</enddate><creator>Schwarzenbacher, Robert</creator><creator>Stenner-Liewen, Frank</creator><creator>Liewen, Heike</creator><creator>Robinson, Howard</creator><creator>Yuan, Hua</creator><creator>Bossy-Wetzel, Ella</creator><creator>Reed, John C</creator><creator>Liddington, Robert C</creator><general>American Society for Biochemistry and Molecular Biology</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>7QL</scope><scope>C1K</scope></search><sort><creationdate>20040709</creationdate><title>Structure of the Chlamydia Protein CADD Reveals a Redox Enzyme That Modulates Host Cell Apoptosis</title><author>Schwarzenbacher, Robert ; Stenner-Liewen, Frank ; Liewen, Heike ; Robinson, Howard ; Yuan, Hua ; Bossy-Wetzel, Ella ; Reed, John C ; Liddington, Robert C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c391t-4b783f6fd3a9302787863c0e60466221aba89279fbceb1a4b64e7363709330f23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Amino Acid Sequence</topic><topic>Apoptosis - physiology</topic><topic>Bacterial Proteins - chemistry</topic><topic>Bacterial Proteins - genetics</topic><topic>Bacterial Proteins - metabolism</topic><topic>Binding Sites</topic><topic>Chlamydia</topic><topic>Chlamydia trachomatis - enzymology</topic><topic>Chlamydia trachomatis - physiology</topic><topic>Crystallography, X-Ray</topic><topic>Humans</topic><topic>Iron - metabolism</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>Mutagenesis, Site-Directed</topic><topic>Oxidation-Reduction</topic><topic>Protein Structure, Tertiary</topic><topic>Sequence Alignment</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schwarzenbacher, Robert</creatorcontrib><creatorcontrib>Stenner-Liewen, Frank</creatorcontrib><creatorcontrib>Liewen, Heike</creatorcontrib><creatorcontrib>Robinson, Howard</creatorcontrib><creatorcontrib>Yuan, Hua</creatorcontrib><creatorcontrib>Bossy-Wetzel, Ella</creatorcontrib><creatorcontrib>Reed, John C</creatorcontrib><creatorcontrib>Liddington, Robert C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schwarzenbacher, Robert</au><au>Stenner-Liewen, Frank</au><au>Liewen, Heike</au><au>Robinson, Howard</au><au>Yuan, Hua</au><au>Bossy-Wetzel, Ella</au><au>Reed, John C</au><au>Liddington, Robert C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structure of the Chlamydia Protein CADD Reveals a Redox Enzyme That Modulates Host Cell Apoptosis</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2004-07-09</date><risdate>2004</risdate><volume>279</volume><issue>28</issue><spage>29320</spage><epage>29324</epage><pages>29320-29324</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>The Chlamydia protein CADD ( C hlamydia protein a ssociating with d eath d omains) has been implicated in the modulation of host cell apoptosis via binding to the death domains of tumor necrosis factor
family receptors. Transfection of CADD into mammalian cells induces apoptosis. Here we present the CADD crystal structure,
which reveals a dimer of seven-helix bundles. Each bundle contains a di-iron center adjacent to an internal cavity, forming
an active site similar to that of methane mono-oxygenase hydrolase. We further show that CADD mutants lacking critical metal-coordinating
residues are substantially less effective in inducing apoptosis but retain their ability to bind to death domains. We conclude
that CADD is a novel redox protein toxin unique to Chlamydia species and propose that both its redox activity and death domain binding ability are required for its biological activity.</abstract><cop>United States</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>15087448</pmid><doi>10.1074/jbc.M401268200</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of biological chemistry, 2004-07, Vol.279 (28), p.29320-29324 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Amino Acid Sequence Apoptosis - physiology Bacterial Proteins - chemistry Bacterial Proteins - genetics Bacterial Proteins - metabolism Binding Sites Chlamydia Chlamydia trachomatis - enzymology Chlamydia trachomatis - physiology Crystallography, X-Ray Humans Iron - metabolism Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Oxidation-Reduction Protein Structure, Tertiary Sequence Alignment |
| title | Structure of the Chlamydia Protein CADD Reveals a Redox Enzyme That Modulates Host Cell Apoptosis |
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