Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex
Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca 2+ and two Cu 2+ ions. The...
Gespeichert in:
| Veröffentlicht in: | Structure 2008-04, Vol.16 (4), p.597-606 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 606 |
|---|---|
| container_issue | 4 |
| container_start_page | 597 |
| container_title | Structure |
| container_volume | 16 |
| creator | Ngo, Jacky Chi Ki Huang, Mingdong Roth, David A. Furie, Barbara C. Furie, Bruce |
| description | Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca
2+ and two Cu
2+ ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface. |
| doi_str_mv | 10.1016/j.str.2008.03.001 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_osti_</sourceid><recordid>TN_cdi_proquest_miscellaneous_901673942</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0969212608000968</els_id><sourcerecordid>70484721</sourcerecordid><originalsourceid>FETCH-LOGICAL-c519t-7561ae28331611d1e6be0341630fcc2e4945bf9a3301ae43ce70be9fe37503563</originalsourceid><addsrcrecordid>eNp9kU1v1DAQhi0EotvCD-CCIg5wSpiJHSeBE1qxNFIlDnyIm-X1TlSvknixnYr-e5xmJTj1ZOnV84w18zL2CqFAQPn-WIToixKgKYAXAPiEbbCpm1xgI5-yDbSyzUss5QW7DOEIAGUF8JxdYCMS3cCGjVt_H6Iesm_RzybOnjLXZ9fzqKdsp010PvvZdd2HrBtPgzU6WjeFrE9xvKVs5_z4EC3SQ7Aq3S-d_2frbOuSTn9esGe9HgK9PL9X7Mfu8_ftdX7z9Uu3_XSTmwrbmNeVRE1lwzlKxAOS3BNwgZJDb0xJohXVvm8155A4wQ3VsKe2J15XwCvJr9ibda4L0apgbCRza9w0kYkKAaTEJkHvVujk3e-ZQlSjDYaGQU_k5qDadOKat6JM5NtHyRpEI-oSE4graLwLwVOvTt6O2t-nT9VSmTqqVJlaKlPAVSohOa_Pw-f9SId_xrmjBHxcAUoXu7Pkl4VoMnSwftnn4Owj4_8C-gWklA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>70484721</pqid></control><display><type>article</type><title>Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><source>Cell Press Free Archives</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Free Full-Text Journals in Chemistry</source><creator>Ngo, Jacky Chi Ki ; Huang, Mingdong ; Roth, David A. ; Furie, Barbara C. ; Furie, Bruce</creator><creatorcontrib>Ngo, Jacky Chi Ki ; Huang, Mingdong ; Roth, David A. ; Furie, Barbara C. ; Furie, Bruce ; Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)</creatorcontrib><description>Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca
2+ and two Cu
2+ ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface.</description><identifier>ISSN: 0969-2126</identifier><identifier>EISSN: 1878-4186</identifier><identifier>DOI: 10.1016/j.str.2008.03.001</identifier><identifier>PMID: 18400180</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; Binding Sites ; Biochemistry ; BLOOD COAGULATION ; CALCIUM IONS ; COPPER IONS ; CRYSTAL STRUCTURE ; Crystallography, X-Ray ; Factor IXa - chemistry ; Factor VIII - chemistry ; Factor VIIIa - chemistry ; HEMOPHILIA ; Human factors ; Humans ; INTERACTIONS ; INTERFACES ; Mathematical models ; MEMBRANES ; Models, Molecular ; Protein Structure, Tertiary ; PROTEINS ; Surface chemistry ; X-rays</subject><ispartof>Structure, 2008-04, Vol.16 (4), p.597-606</ispartof><rights>2008 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c519t-7561ae28331611d1e6be0341630fcc2e4945bf9a3301ae43ce70be9fe37503563</citedby><cites>FETCH-LOGICAL-c519t-7561ae28331611d1e6be0341630fcc2e4945bf9a3301ae43ce70be9fe37503563</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0969212608000968$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,881,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18400180$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/1006618$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Ngo, Jacky Chi Ki</creatorcontrib><creatorcontrib>Huang, Mingdong</creatorcontrib><creatorcontrib>Roth, David A.</creatorcontrib><creatorcontrib>Furie, Barbara C.</creatorcontrib><creatorcontrib>Furie, Bruce</creatorcontrib><creatorcontrib>Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)</creatorcontrib><title>Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex</title><title>Structure</title><addtitle>Structure</addtitle><description>Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca
2+ and two Cu
2+ ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>Binding Sites</subject><subject>Biochemistry</subject><subject>BLOOD COAGULATION</subject><subject>CALCIUM IONS</subject><subject>COPPER IONS</subject><subject>CRYSTAL STRUCTURE</subject><subject>Crystallography, X-Ray</subject><subject>Factor IXa - chemistry</subject><subject>Factor VIII - chemistry</subject><subject>Factor VIIIa - chemistry</subject><subject>HEMOPHILIA</subject><subject>Human factors</subject><subject>Humans</subject><subject>INTERACTIONS</subject><subject>INTERFACES</subject><subject>Mathematical models</subject><subject>MEMBRANES</subject><subject>Models, Molecular</subject><subject>Protein Structure, Tertiary</subject><subject>PROTEINS</subject><subject>Surface chemistry</subject><subject>X-rays</subject><issn>0969-2126</issn><issn>1878-4186</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQhi0EotvCD-CCIg5wSpiJHSeBE1qxNFIlDnyIm-X1TlSvknixnYr-e5xmJTj1ZOnV84w18zL2CqFAQPn-WIToixKgKYAXAPiEbbCpm1xgI5-yDbSyzUss5QW7DOEIAGUF8JxdYCMS3cCGjVt_H6Iesm_RzybOnjLXZ9fzqKdsp010PvvZdd2HrBtPgzU6WjeFrE9xvKVs5_z4EC3SQ7Aq3S-d_2frbOuSTn9esGe9HgK9PL9X7Mfu8_ftdX7z9Uu3_XSTmwrbmNeVRE1lwzlKxAOS3BNwgZJDb0xJohXVvm8155A4wQ3VsKe2J15XwCvJr9ibda4L0apgbCRza9w0kYkKAaTEJkHvVujk3e-ZQlSjDYaGQU_k5qDadOKat6JM5NtHyRpEI-oSE4graLwLwVOvTt6O2t-nT9VSmTqqVJlaKlPAVSohOa_Pw-f9SId_xrmjBHxcAUoXu7Pkl4VoMnSwftnn4Owj4_8C-gWklA</recordid><startdate>20080401</startdate><enddate>20080401</enddate><creator>Ngo, Jacky Chi Ki</creator><creator>Huang, Mingdong</creator><creator>Roth, David A.</creator><creator>Furie, Barbara C.</creator><creator>Furie, Bruce</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><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><scope>7U5</scope><scope>8FD</scope><scope>F28</scope><scope>FR3</scope><scope>L7M</scope><scope>OTOTI</scope></search><sort><creationdate>20080401</creationdate><title>Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex</title><author>Ngo, Jacky Chi Ki ; Huang, Mingdong ; Roth, David A. ; Furie, Barbara C. ; Furie, Bruce</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c519t-7561ae28331611d1e6be0341630fcc2e4945bf9a3301ae43ce70be9fe37503563</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>Binding Sites</topic><topic>Biochemistry</topic><topic>BLOOD COAGULATION</topic><topic>CALCIUM IONS</topic><topic>COPPER IONS</topic><topic>CRYSTAL STRUCTURE</topic><topic>Crystallography, X-Ray</topic><topic>Factor IXa - chemistry</topic><topic>Factor VIII - chemistry</topic><topic>Factor VIIIa - chemistry</topic><topic>HEMOPHILIA</topic><topic>Human factors</topic><topic>Humans</topic><topic>INTERACTIONS</topic><topic>INTERFACES</topic><topic>Mathematical models</topic><topic>MEMBRANES</topic><topic>Models, Molecular</topic><topic>Protein Structure, Tertiary</topic><topic>PROTEINS</topic><topic>Surface chemistry</topic><topic>X-rays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ngo, Jacky Chi Ki</creatorcontrib><creatorcontrib>Huang, Mingdong</creatorcontrib><creatorcontrib>Roth, David A.</creatorcontrib><creatorcontrib>Furie, Barbara C.</creatorcontrib><creatorcontrib>Furie, Bruce</creatorcontrib><creatorcontrib>Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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><collection>Solid State and Superconductivity Abstracts</collection><collection>Technology Research Database</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>OSTI.GOV</collection><jtitle>Structure</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ngo, Jacky Chi Ki</au><au>Huang, Mingdong</au><au>Roth, David A.</au><au>Furie, Barbara C.</au><au>Furie, Bruce</au><aucorp>Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex</atitle><jtitle>Structure</jtitle><addtitle>Structure</addtitle><date>2008-04-01</date><risdate>2008</risdate><volume>16</volume><issue>4</issue><spage>597</spage><epage>606</epage><pages>597-606</pages><issn>0969-2126</issn><eissn>1878-4186</eissn><abstract>Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca
2+ and two Cu
2+ ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>18400180</pmid><doi>10.1016/j.str.2008.03.001</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0969-2126 |
| ispartof | Structure, 2008-04, Vol.16 (4), p.597-606 |
| issn | 0969-2126 1878-4186 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_901673942 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete; Cell Press Free Archives; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | 60 APPLIED LIFE SCIENCES Binding Sites Biochemistry BLOOD COAGULATION CALCIUM IONS COPPER IONS CRYSTAL STRUCTURE Crystallography, X-Ray Factor IXa - chemistry Factor VIII - chemistry Factor VIIIa - chemistry HEMOPHILIA Human factors Humans INTERACTIONS INTERFACES Mathematical models MEMBRANES Models, Molecular Protein Structure, Tertiary PROTEINS Surface chemistry X-rays |
| title | Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T17%3A57%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_osti_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Crystal%20Structure%20of%20Human%20Factor%20VIII:%20Implications%20for%20the%20Formation%20of%20the%20Factor%20IXa-Factor%20VIIIa%20Complex&rft.jtitle=Structure&rft.au=Ngo,%20Jacky%20Chi%20Ki&rft.aucorp=Argonne%20National%20Lab.%20(ANL),%20Argonne,%20IL%20(United%20States).%20Advanced%20Photon%20Source%20(APS)&rft.date=2008-04-01&rft.volume=16&rft.issue=4&rft.spage=597&rft.epage=606&rft.pages=597-606&rft.issn=0969-2126&rft.eissn=1878-4186&rft_id=info:doi/10.1016/j.str.2008.03.001&rft_dat=%3Cproquest_osti_%3E70484721%3C/proquest_osti_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=70484721&rft_id=info:pmid/18400180&rft_els_id=S0969212608000968&rfr_iscdi=true |