The promiscuous binding of the Fyn SH3 domain to a peptide from the NS5A protein
The hepatitis C virus nonstructural 5A (NS5A) protein is a large zinc‐binding phosphoprotein that plays an important role in viral RNA replication and is involved in altering signal transduction pathways in the host cell. This protein interacts with Fyn tyrosine kinase in vivo and regulates its kina...
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| Veröffentlicht in: | Acta crystallographica. Section D, Biological crystallography. Biological crystallography., 2012-08, Vol.68 (8), p.1030-1040 |
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| container_title | Acta crystallographica. Section D, Biological crystallography. |
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| creator | Martin-Garcia, Jose Manuel Luque, Irene Ruiz-Sanz, Javier Camara-Artigas, Ana |
| description | The hepatitis C virus nonstructural 5A (NS5A) protein is a large zinc‐binding phosphoprotein that plays an important role in viral RNA replication and is involved in altering signal transduction pathways in the host cell. This protein interacts with Fyn tyrosine kinase in vivo and regulates its kinase activity. The 1.5 Å resolution crystal structure of a complex between the SH3 domain of the Fyn tyrosine kinase and the C‐terminal proline‐rich motif of the NS5A‐derived peptide APPIPPPRRKR has been solved. Crystals were obtained in the presence of ZnCl2 and belonged to the tetragonal space group P41212. The asymmetric unit is composed of four SH3 domains and two NS5A peptide molecules; only three of the domain molecules contain a bound peptide, while the fourth molecule seems to correspond to a free form of the domain. Additionally, two of the SH3 domains are bound to the same peptide chain and form a ternary complex. The proline‐rich motif present in the NS5A protein seems to be important for RNA replication and virus assembly, and the promiscuous interaction of the Fyn SH3 domain with the NS5A C‐terminal proline‐rich peptide found in this crystallographic structure may be important in the virus infection cycle. |
| doi_str_mv | 10.1107/S0907444912019798 |
| format | Article |
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This protein interacts with Fyn tyrosine kinase in vivo and regulates its kinase activity. The 1.5 Å resolution crystal structure of a complex between the SH3 domain of the Fyn tyrosine kinase and the C‐terminal proline‐rich motif of the NS5A‐derived peptide APPIPPPRRKR has been solved. Crystals were obtained in the presence of ZnCl2 and belonged to the tetragonal space group P41212. The asymmetric unit is composed of four SH3 domains and two NS5A peptide molecules; only three of the domain molecules contain a bound peptide, while the fourth molecule seems to correspond to a free form of the domain. Additionally, two of the SH3 domains are bound to the same peptide chain and form a ternary complex. The proline‐rich motif present in the NS5A protein seems to be important for RNA replication and virus assembly, and the promiscuous interaction of the Fyn SH3 domain with the NS5A C‐terminal proline‐rich peptide found in this crystallographic structure may be important in the virus infection cycle.</description><identifier>ISSN: 1399-0047</identifier><identifier>ISSN: 0907-4449</identifier><identifier>EISSN: 1399-0047</identifier><identifier>DOI: 10.1107/S0907444912019798</identifier><identifier>PMID: 22868769</identifier><language>eng</language><publisher>5 Abbey Square, Chester, Cheshire CH1 2HU, England: International Union of Crystallography</publisher><subject>Amino Acid Motifs ; Binding ; Calorimetry - methods ; Cloning, Molecular ; Crystal structure ; Crystallography, X-Ray - methods ; Fyn tyrosine kinase ; Hepacivirus - metabolism ; hepatitis C virus ; Humans ; Kinases ; Ligands ; Light ; NS5A ; Peptides ; Peptides - chemistry ; Proline - chemistry ; proline-rich motifs ; Protein Binding ; Proteins ; Proto-Oncogene Proteins c-fyn - chemistry ; Replication ; Ribonucleic acids ; Scattering, Radiation ; SH3 domains ; Signal Transduction ; src Homology Domains - genetics ; Tyrosine ; Viral Nonstructural Proteins - chemistry ; Zinc - chemistry</subject><ispartof>Acta crystallographica. Section D, Biological crystallography., 2012-08, Vol.68 (8), p.1030-1040</ispartof><rights>International Union of Crystallography, 2012</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4492-acb73304ffd5f6c0614b84fe033f012915413a6717a26bc22add63f2985a15a13</citedby><cites>FETCH-LOGICAL-c4492-acb73304ffd5f6c0614b84fe033f012915413a6717a26bc22add63f2985a15a13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1107%2FS0907444912019798$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1107%2FS0907444912019798$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22868769$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Martin-Garcia, Jose Manuel</creatorcontrib><creatorcontrib>Luque, Irene</creatorcontrib><creatorcontrib>Ruiz-Sanz, Javier</creatorcontrib><creatorcontrib>Camara-Artigas, Ana</creatorcontrib><title>The promiscuous binding of the Fyn SH3 domain to a peptide from the NS5A protein</title><title>Acta crystallographica. Section D, Biological crystallography.</title><addtitle>Acta Cryst. D</addtitle><description>The hepatitis C virus nonstructural 5A (NS5A) protein is a large zinc‐binding phosphoprotein that plays an important role in viral RNA replication and is involved in altering signal transduction pathways in the host cell. This protein interacts with Fyn tyrosine kinase in vivo and regulates its kinase activity. The 1.5 Å resolution crystal structure of a complex between the SH3 domain of the Fyn tyrosine kinase and the C‐terminal proline‐rich motif of the NS5A‐derived peptide APPIPPPRRKR has been solved. Crystals were obtained in the presence of ZnCl2 and belonged to the tetragonal space group P41212. The asymmetric unit is composed of four SH3 domains and two NS5A peptide molecules; only three of the domain molecules contain a bound peptide, while the fourth molecule seems to correspond to a free form of the domain. Additionally, two of the SH3 domains are bound to the same peptide chain and form a ternary complex. The proline‐rich motif present in the NS5A protein seems to be important for RNA replication and virus assembly, and the promiscuous interaction of the Fyn SH3 domain with the NS5A C‐terminal proline‐rich peptide found in this crystallographic structure may be important in the virus infection cycle.</description><subject>Amino Acid Motifs</subject><subject>Binding</subject><subject>Calorimetry - methods</subject><subject>Cloning, Molecular</subject><subject>Crystal structure</subject><subject>Crystallography, X-Ray - methods</subject><subject>Fyn tyrosine kinase</subject><subject>Hepacivirus - metabolism</subject><subject>hepatitis C virus</subject><subject>Humans</subject><subject>Kinases</subject><subject>Ligands</subject><subject>Light</subject><subject>NS5A</subject><subject>Peptides</subject><subject>Peptides - chemistry</subject><subject>Proline - chemistry</subject><subject>proline-rich motifs</subject><subject>Protein Binding</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-fyn - chemistry</subject><subject>Replication</subject><subject>Ribonucleic acids</subject><subject>Scattering, Radiation</subject><subject>SH3 domains</subject><subject>Signal Transduction</subject><subject>src Homology Domains - genetics</subject><subject>Tyrosine</subject><subject>Viral Nonstructural Proteins - chemistry</subject><subject>Zinc - chemistry</subject><issn>1399-0047</issn><issn>0907-4449</issn><issn>1399-0047</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUU1P4zAUtBArPrr7A7ggS1y4hLX9HDs-VnwFiQWkdsVyspzEBkOblDgR9N_jUrZCcADJ0rPkmXkzHoR2KDmglMjfI6KI5JwryghVUmVraIuCUgkhXK6_u2-i7RDuCSGMgdxAm4xlIpNCbaGr8Z3Fs7aZ-lD2TR9w4evK17e4cbiLTyfzGo9ywFUzNb7GXYMNntlZ5yuLXaS9gi5G6XAh0llf_0Q_nJkE--ttDtDfk-PxYZ6cX56eHQ7PkzL6ZYkpCwlAuHNV6kRJBOVFxp0lAI5QpmjKKRghqTRMFCVjpqoEOKay1NB4YID2l7px72NvQ6cXEexkYmobc2hKMsYol_AdKDAJGcTPGaC9D9D7pm_rGERTAIiu0jgHiC5RZduE0FqnZ62fmnYepfSiGf2pmcjZfVPui6mtVoz_VURAtgQ8-Ymdf62ohzdHf_KUiIXrZEn1obPPK6ppH7SQIFN9fXGqRzmTOft3pa_hBaMDo98</recordid><startdate>20120801</startdate><enddate>20120801</enddate><creator>Martin-Garcia, Jose Manuel</creator><creator>Luque, Irene</creator><creator>Ruiz-Sanz, Javier</creator><creator>Camara-Artigas, Ana</creator><general>International Union of Crystallography</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>7QP</scope><scope>7SP</scope><scope>7SR</scope><scope>7TK</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>H8D</scope><scope>JG9</scope><scope>L7M</scope><scope>7X8</scope></search><sort><creationdate>20120801</creationdate><title>The promiscuous binding of the Fyn SH3 domain to a peptide from the NS5A protein</title><author>Martin-Garcia, Jose Manuel ; Luque, Irene ; Ruiz-Sanz, Javier ; Camara-Artigas, Ana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4492-acb73304ffd5f6c0614b84fe033f012915413a6717a26bc22add63f2985a15a13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Amino Acid Motifs</topic><topic>Binding</topic><topic>Calorimetry - methods</topic><topic>Cloning, Molecular</topic><topic>Crystal structure</topic><topic>Crystallography, X-Ray - methods</topic><topic>Fyn tyrosine kinase</topic><topic>Hepacivirus - metabolism</topic><topic>hepatitis C virus</topic><topic>Humans</topic><topic>Kinases</topic><topic>Ligands</topic><topic>Light</topic><topic>NS5A</topic><topic>Peptides</topic><topic>Peptides - chemistry</topic><topic>Proline - chemistry</topic><topic>proline-rich motifs</topic><topic>Protein Binding</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-fyn - chemistry</topic><topic>Replication</topic><topic>Ribonucleic acids</topic><topic>Scattering, Radiation</topic><topic>SH3 domains</topic><topic>Signal Transduction</topic><topic>src Homology Domains - genetics</topic><topic>Tyrosine</topic><topic>Viral Nonstructural Proteins - chemistry</topic><topic>Zinc - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Martin-Garcia, Jose Manuel</creatorcontrib><creatorcontrib>Luque, Irene</creatorcontrib><creatorcontrib>Ruiz-Sanz, Javier</creatorcontrib><creatorcontrib>Camara-Artigas, Ana</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Aerospace Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>MEDLINE - Academic</collection><jtitle>Acta crystallographica. Section D, Biological crystallography.</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Martin-Garcia, Jose Manuel</au><au>Luque, Irene</au><au>Ruiz-Sanz, Javier</au><au>Camara-Artigas, Ana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The promiscuous binding of the Fyn SH3 domain to a peptide from the NS5A protein</atitle><jtitle>Acta crystallographica. Section D, Biological crystallography.</jtitle><addtitle>Acta Cryst. D</addtitle><date>2012-08-01</date><risdate>2012</risdate><volume>68</volume><issue>8</issue><spage>1030</spage><epage>1040</epage><pages>1030-1040</pages><issn>1399-0047</issn><issn>0907-4449</issn><eissn>1399-0047</eissn><abstract>The hepatitis C virus nonstructural 5A (NS5A) protein is a large zinc‐binding phosphoprotein that plays an important role in viral RNA replication and is involved in altering signal transduction pathways in the host cell. This protein interacts with Fyn tyrosine kinase in vivo and regulates its kinase activity. The 1.5 Å resolution crystal structure of a complex between the SH3 domain of the Fyn tyrosine kinase and the C‐terminal proline‐rich motif of the NS5A‐derived peptide APPIPPPRRKR has been solved. Crystals were obtained in the presence of ZnCl2 and belonged to the tetragonal space group P41212. The asymmetric unit is composed of four SH3 domains and two NS5A peptide molecules; only three of the domain molecules contain a bound peptide, while the fourth molecule seems to correspond to a free form of the domain. Additionally, two of the SH3 domains are bound to the same peptide chain and form a ternary complex. The proline‐rich motif present in the NS5A protein seems to be important for RNA replication and virus assembly, and the promiscuous interaction of the Fyn SH3 domain with the NS5A C‐terminal proline‐rich peptide found in this crystallographic structure may be important in the virus infection cycle.</abstract><cop>5 Abbey Square, Chester, Cheshire CH1 2HU, England</cop><pub>International Union of Crystallography</pub><pmid>22868769</pmid><doi>10.1107/S0907444912019798</doi><tpages>11</tpages></addata></record> |
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| subjects | Amino Acid Motifs Binding Calorimetry - methods Cloning, Molecular Crystal structure Crystallography, X-Ray - methods Fyn tyrosine kinase Hepacivirus - metabolism hepatitis C virus Humans Kinases Ligands Light NS5A Peptides Peptides - chemistry Proline - chemistry proline-rich motifs Protein Binding Proteins Proto-Oncogene Proteins c-fyn - chemistry Replication Ribonucleic acids Scattering, Radiation SH3 domains Signal Transduction src Homology Domains - genetics Tyrosine Viral Nonstructural Proteins - chemistry Zinc - chemistry |
| title | The promiscuous binding of the Fyn SH3 domain to a peptide from the NS5A protein |
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