The Extended Conformation of the 2.9-Å Crystal Structure of the Three-PASTA Domain of a Ser/Thr Kinase from the Human Pathogen Staphylococcus aureus
PASTA ( penicillin-binding protein and serine/ threonine kinase associated) modules are found in penicillin-binding proteins and bacterial serine/threonine kinases mainly from Gram-positive Firmicutes and Actinobacteria. They may act as extracellular sensors by binding peptidoglycan fragments. We re...
Gespeichert in:
| Veröffentlicht in: | Journal of molecular biology 2010-12, Vol.404 (5), p.847-858 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 858 |
|---|---|
| container_issue | 5 |
| container_start_page | 847 |
| container_title | Journal of molecular biology |
| container_volume | 404 |
| creator | Paracuellos, Patricia Ballandras, Allison Robert, Xavier Kahn, Richard Hervé, Mireille Mengin-Lecreulx, Dominique Cozzone, Alain J. Duclos, Bertrand Gouet, Patrice |
| description | PASTA (
penicillin-binding protein
and
serine/
threonine kinase
associated) modules are found in penicillin-binding proteins and bacterial serine/threonine kinases mainly from Gram-positive Firmicutes and Actinobacteria. They may act as extracellular sensors by binding peptidoglycan fragments. We report here the first crystal structure of a multiple-PASTA domain from Ser/Thr kinase, that of the protein serine/threonine kinase 1 (Stk1) from the Firmicute
Staphylococcus aureus. The extended conformation of the three PASTA subunits differs strongly from the compact conformation observed in the two-PASTA domain of penicillin-binding protein PBP2x, whereas linear conformations were also reported for two-subunit fragments of the four-PASTA domain of the Actinobacteria
Mycobacterium tuberculosis studied by liquid NMR. Thus, a stretched organization appears to be the signature of modular PASTA domains in Ser/Thr kinases. Signal transduction to the kinase domain is supposed to occur
via dimerization and ligand binding. A conserved X-shaped crystallographic dimer stabilized by intermolecular interactions between the second PASTA subunits of each monomer is observed in the two crystal forms of Stk1 that we managed to crystallize. Extracellular PASTA domains are composed of at least two subunits, and this molecular assembly is a plausible candidate for the biological dimer. We have also performed docking experiments, which predict that the hinge regions of the PASTA domain can accommodate peptidoglycan. Finally, a three-dimensional homology molecular model of full-length Stk1 was generated, suggesting an interaction between the kinase domain and the cytoplasmic face of the plasma membrane
via a eukaryotic-like juxtamembrane domain. A comprehensive activation mechanism for bacterial Ser/Thr kinases is proposed with the support of these structural data.
▪
► Structural features in hinge regions promoting an extended conformation. ► Docking and ITC experiments support PASTA–peptidoglycan binding. ► Full-length model suggesting interactions between transmembrane and kinase domains. |
| doi_str_mv | 10.1016/j.jmb.2010.10.012 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_hal_p</sourceid><recordid>TN_cdi_hal_primary_oai_HAL_hal_04246133v1</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0022283610011095</els_id><sourcerecordid>812133534</sourcerecordid><originalsourceid>FETCH-LOGICAL-c301t-bd22d80dfc6042134f8e15ae82f112b43086f65c5c4b521215149b1c155a327b3</originalsourceid><addsrcrecordid>eNp9kcGO0zAQhi0EYsvCA3BBviEOyXrsJDjiVJVdiqjESi1ny3Em1FUSF9tZ0QfgEfaJeDHcdnePnCzP_813mJ-Qt8ByYFBd7fLd0OScnf45A_6MzIDJOpOVkM_JjDHOMy5FdUFehbBjjJWikC_JBWd1VUJdz8j9Zov0-nfEscWWLtzYOT_oaN1IXUdjCnleZ3__0IU_hKh7uo5-MnHy-Jhvth4xu52vN3P62Q3anjY1XaO_Shn9ZkcdkHbeDSd-OQ16pLc6bt1PHJNP77eH3hlnzBSoTuYpvCYvOt0HfPPwXpIfN9ebxTJbff_ydTFfZUYwiFnTct5K1namYgUHUXQSodQoeQfAm0IwWXVVaUpTNCUHDiUUdQMGylIL_rERl-TD2bvVvdp7O2h_UE5btZyv1HGWtEUFQtxBYt-f2b13vyYMUQ02GOx7PaKbgpLJL0Q6cCLhTBrvQvDYPamBqWNxaqdScepY3HGUiks77x7sUzNg-7Tx2FQCPp0BTPe4s-hVMBZHg631aKJqnf2P_h_DJadi</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>812133534</pqid></control><display><type>article</type><title>The Extended Conformation of the 2.9-Å Crystal Structure of the Three-PASTA Domain of a Ser/Thr Kinase from the Human Pathogen Staphylococcus aureus</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Paracuellos, Patricia ; Ballandras, Allison ; Robert, Xavier ; Kahn, Richard ; Hervé, Mireille ; Mengin-Lecreulx, Dominique ; Cozzone, Alain J. ; Duclos, Bertrand ; Gouet, Patrice</creator><creatorcontrib>Paracuellos, Patricia ; Ballandras, Allison ; Robert, Xavier ; Kahn, Richard ; Hervé, Mireille ; Mengin-Lecreulx, Dominique ; Cozzone, Alain J. ; Duclos, Bertrand ; Gouet, Patrice</creatorcontrib><description>PASTA (
penicillin-binding protein
and
serine/
threonine kinase
associated) modules are found in penicillin-binding proteins and bacterial serine/threonine kinases mainly from Gram-positive Firmicutes and Actinobacteria. They may act as extracellular sensors by binding peptidoglycan fragments. We report here the first crystal structure of a multiple-PASTA domain from Ser/Thr kinase, that of the protein serine/threonine kinase 1 (Stk1) from the Firmicute
Staphylococcus aureus. The extended conformation of the three PASTA subunits differs strongly from the compact conformation observed in the two-PASTA domain of penicillin-binding protein PBP2x, whereas linear conformations were also reported for two-subunit fragments of the four-PASTA domain of the Actinobacteria
Mycobacterium tuberculosis studied by liquid NMR. Thus, a stretched organization appears to be the signature of modular PASTA domains in Ser/Thr kinases. Signal transduction to the kinase domain is supposed to occur
via dimerization and ligand binding. A conserved X-shaped crystallographic dimer stabilized by intermolecular interactions between the second PASTA subunits of each monomer is observed in the two crystal forms of Stk1 that we managed to crystallize. Extracellular PASTA domains are composed of at least two subunits, and this molecular assembly is a plausible candidate for the biological dimer. We have also performed docking experiments, which predict that the hinge regions of the PASTA domain can accommodate peptidoglycan. Finally, a three-dimensional homology molecular model of full-length Stk1 was generated, suggesting an interaction between the kinase domain and the cytoplasmic face of the plasma membrane
via a eukaryotic-like juxtamembrane domain. A comprehensive activation mechanism for bacterial Ser/Thr kinases is proposed with the support of these structural data.
▪
► Structural features in hinge regions promoting an extended conformation. ► Docking and ITC experiments support PASTA–peptidoglycan binding. ► Full-length model suggesting interactions between transmembrane and kinase domains.</description><identifier>ISSN: 0022-2836</identifier><identifier>EISSN: 1089-8638</identifier><identifier>DOI: 10.1016/j.jmb.2010.10.012</identifier><identifier>PMID: 20965199</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Amino Acid Sequence ; crystal structure ; Crystallography, X-Ray ; Life Sciences ; Models, Molecular ; Molecular Sequence Data ; PASTA domain ; Protein Binding ; Protein Conformation ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases - chemistry ; serine/threonine kinase 1 ; Staphylococcus aureus ; Staphylococcus aureus - enzymology ; Virulence Factors - chemistry</subject><ispartof>Journal of molecular biology, 2010-12, Vol.404 (5), p.847-858</ispartof><rights>2010 Elsevier Ltd</rights><rights>Copyright © 2010 Elsevier Ltd. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c301t-bd22d80dfc6042134f8e15ae82f112b43086f65c5c4b521215149b1c155a327b3</citedby><cites>FETCH-LOGICAL-c301t-bd22d80dfc6042134f8e15ae82f112b43086f65c5c4b521215149b1c155a327b3</cites><orcidid>0000-0001-9485-6157</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jmb.2010.10.012$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20965199$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-04246133$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Paracuellos, Patricia</creatorcontrib><creatorcontrib>Ballandras, Allison</creatorcontrib><creatorcontrib>Robert, Xavier</creatorcontrib><creatorcontrib>Kahn, Richard</creatorcontrib><creatorcontrib>Hervé, Mireille</creatorcontrib><creatorcontrib>Mengin-Lecreulx, Dominique</creatorcontrib><creatorcontrib>Cozzone, Alain J.</creatorcontrib><creatorcontrib>Duclos, Bertrand</creatorcontrib><creatorcontrib>Gouet, Patrice</creatorcontrib><title>The Extended Conformation of the 2.9-Å Crystal Structure of the Three-PASTA Domain of a Ser/Thr Kinase from the Human Pathogen Staphylococcus aureus</title><title>Journal of molecular biology</title><addtitle>J Mol Biol</addtitle><description>PASTA (
penicillin-binding protein
and
serine/
threonine kinase
associated) modules are found in penicillin-binding proteins and bacterial serine/threonine kinases mainly from Gram-positive Firmicutes and Actinobacteria. They may act as extracellular sensors by binding peptidoglycan fragments. We report here the first crystal structure of a multiple-PASTA domain from Ser/Thr kinase, that of the protein serine/threonine kinase 1 (Stk1) from the Firmicute
Staphylococcus aureus. The extended conformation of the three PASTA subunits differs strongly from the compact conformation observed in the two-PASTA domain of penicillin-binding protein PBP2x, whereas linear conformations were also reported for two-subunit fragments of the four-PASTA domain of the Actinobacteria
Mycobacterium tuberculosis studied by liquid NMR. Thus, a stretched organization appears to be the signature of modular PASTA domains in Ser/Thr kinases. Signal transduction to the kinase domain is supposed to occur
via dimerization and ligand binding. A conserved X-shaped crystallographic dimer stabilized by intermolecular interactions between the second PASTA subunits of each monomer is observed in the two crystal forms of Stk1 that we managed to crystallize. Extracellular PASTA domains are composed of at least two subunits, and this molecular assembly is a plausible candidate for the biological dimer. We have also performed docking experiments, which predict that the hinge regions of the PASTA domain can accommodate peptidoglycan. Finally, a three-dimensional homology molecular model of full-length Stk1 was generated, suggesting an interaction between the kinase domain and the cytoplasmic face of the plasma membrane
via a eukaryotic-like juxtamembrane domain. A comprehensive activation mechanism for bacterial Ser/Thr kinases is proposed with the support of these structural data.
▪
► Structural features in hinge regions promoting an extended conformation. ► Docking and ITC experiments support PASTA–peptidoglycan binding. ► Full-length model suggesting interactions between transmembrane and kinase domains.</description><subject>Amino Acid Sequence</subject><subject>crystal structure</subject><subject>Crystallography, X-Ray</subject><subject>Life Sciences</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>PASTA domain</subject><subject>Protein Binding</subject><subject>Protein Conformation</subject><subject>Protein Multimerization</subject><subject>Protein Structure, Quaternary</subject><subject>Protein Structure, Secondary</subject><subject>Protein Structure, Tertiary</subject><subject>Protein-Serine-Threonine Kinases - chemistry</subject><subject>serine/threonine kinase 1</subject><subject>Staphylococcus aureus</subject><subject>Staphylococcus aureus - enzymology</subject><subject>Virulence Factors - chemistry</subject><issn>0022-2836</issn><issn>1089-8638</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcGO0zAQhi0EYsvCA3BBviEOyXrsJDjiVJVdiqjESi1ny3Em1FUSF9tZ0QfgEfaJeDHcdnePnCzP_813mJ-Qt8ByYFBd7fLd0OScnf45A_6MzIDJOpOVkM_JjDHOMy5FdUFehbBjjJWikC_JBWd1VUJdz8j9Zov0-nfEscWWLtzYOT_oaN1IXUdjCnleZ3__0IU_hKh7uo5-MnHy-Jhvth4xu52vN3P62Q3anjY1XaO_Shn9ZkcdkHbeDSd-OQ16pLc6bt1PHJNP77eH3hlnzBSoTuYpvCYvOt0HfPPwXpIfN9ebxTJbff_ydTFfZUYwiFnTct5K1namYgUHUXQSodQoeQfAm0IwWXVVaUpTNCUHDiUUdQMGylIL_rERl-TD2bvVvdp7O2h_UE5btZyv1HGWtEUFQtxBYt-f2b13vyYMUQ02GOx7PaKbgpLJL0Q6cCLhTBrvQvDYPamBqWNxaqdScepY3HGUiks77x7sUzNg-7Tx2FQCPp0BTPe4s-hVMBZHg631aKJqnf2P_h_DJadi</recordid><startdate>20101217</startdate><enddate>20101217</enddate><creator>Paracuellos, Patricia</creator><creator>Ballandras, Allison</creator><creator>Robert, Xavier</creator><creator>Kahn, Richard</creator><creator>Hervé, Mireille</creator><creator>Mengin-Lecreulx, Dominique</creator><creator>Cozzone, Alain J.</creator><creator>Duclos, Bertrand</creator><creator>Gouet, Patrice</creator><general>Elsevier Ltd</general><general>Elsevier</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><scope>1XC</scope><orcidid>https://orcid.org/0000-0001-9485-6157</orcidid></search><sort><creationdate>20101217</creationdate><title>The Extended Conformation of the 2.9-Å Crystal Structure of the Three-PASTA Domain of a Ser/Thr Kinase from the Human Pathogen Staphylococcus aureus</title><author>Paracuellos, Patricia ; Ballandras, Allison ; Robert, Xavier ; Kahn, Richard ; Hervé, Mireille ; Mengin-Lecreulx, Dominique ; Cozzone, Alain J. ; Duclos, Bertrand ; Gouet, Patrice</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c301t-bd22d80dfc6042134f8e15ae82f112b43086f65c5c4b521215149b1c155a327b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Amino Acid Sequence</topic><topic>crystal structure</topic><topic>Crystallography, X-Ray</topic><topic>Life Sciences</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>PASTA domain</topic><topic>Protein Binding</topic><topic>Protein Conformation</topic><topic>Protein Multimerization</topic><topic>Protein Structure, Quaternary</topic><topic>Protein Structure, Secondary</topic><topic>Protein Structure, Tertiary</topic><topic>Protein-Serine-Threonine Kinases - chemistry</topic><topic>serine/threonine kinase 1</topic><topic>Staphylococcus aureus</topic><topic>Staphylococcus aureus - enzymology</topic><topic>Virulence Factors - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Paracuellos, Patricia</creatorcontrib><creatorcontrib>Ballandras, Allison</creatorcontrib><creatorcontrib>Robert, Xavier</creatorcontrib><creatorcontrib>Kahn, Richard</creatorcontrib><creatorcontrib>Hervé, Mireille</creatorcontrib><creatorcontrib>Mengin-Lecreulx, Dominique</creatorcontrib><creatorcontrib>Cozzone, Alain J.</creatorcontrib><creatorcontrib>Duclos, Bertrand</creatorcontrib><creatorcontrib>Gouet, Patrice</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><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Journal of molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Paracuellos, Patricia</au><au>Ballandras, Allison</au><au>Robert, Xavier</au><au>Kahn, Richard</au><au>Hervé, Mireille</au><au>Mengin-Lecreulx, Dominique</au><au>Cozzone, Alain J.</au><au>Duclos, Bertrand</au><au>Gouet, Patrice</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Extended Conformation of the 2.9-Å Crystal Structure of the Three-PASTA Domain of a Ser/Thr Kinase from the Human Pathogen Staphylococcus aureus</atitle><jtitle>Journal of molecular biology</jtitle><addtitle>J Mol Biol</addtitle><date>2010-12-17</date><risdate>2010</risdate><volume>404</volume><issue>5</issue><spage>847</spage><epage>858</epage><pages>847-858</pages><issn>0022-2836</issn><eissn>1089-8638</eissn><abstract>PASTA (
penicillin-binding protein
and
serine/
threonine kinase
associated) modules are found in penicillin-binding proteins and bacterial serine/threonine kinases mainly from Gram-positive Firmicutes and Actinobacteria. They may act as extracellular sensors by binding peptidoglycan fragments. We report here the first crystal structure of a multiple-PASTA domain from Ser/Thr kinase, that of the protein serine/threonine kinase 1 (Stk1) from the Firmicute
Staphylococcus aureus. The extended conformation of the three PASTA subunits differs strongly from the compact conformation observed in the two-PASTA domain of penicillin-binding protein PBP2x, whereas linear conformations were also reported for two-subunit fragments of the four-PASTA domain of the Actinobacteria
Mycobacterium tuberculosis studied by liquid NMR. Thus, a stretched organization appears to be the signature of modular PASTA domains in Ser/Thr kinases. Signal transduction to the kinase domain is supposed to occur
via dimerization and ligand binding. A conserved X-shaped crystallographic dimer stabilized by intermolecular interactions between the second PASTA subunits of each monomer is observed in the two crystal forms of Stk1 that we managed to crystallize. Extracellular PASTA domains are composed of at least two subunits, and this molecular assembly is a plausible candidate for the biological dimer. We have also performed docking experiments, which predict that the hinge regions of the PASTA domain can accommodate peptidoglycan. Finally, a three-dimensional homology molecular model of full-length Stk1 was generated, suggesting an interaction between the kinase domain and the cytoplasmic face of the plasma membrane
via a eukaryotic-like juxtamembrane domain. A comprehensive activation mechanism for bacterial Ser/Thr kinases is proposed with the support of these structural data.
▪
► Structural features in hinge regions promoting an extended conformation. ► Docking and ITC experiments support PASTA–peptidoglycan binding. ► Full-length model suggesting interactions between transmembrane and kinase domains.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>20965199</pmid><doi>10.1016/j.jmb.2010.10.012</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-9485-6157</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2836 |
| ispartof | Journal of molecular biology, 2010-12, Vol.404 (5), p.847-858 |
| issn | 0022-2836 1089-8638 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_04246133v1 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Amino Acid Sequence crystal structure Crystallography, X-Ray Life Sciences Models, Molecular Molecular Sequence Data PASTA domain Protein Binding Protein Conformation Protein Multimerization Protein Structure, Quaternary Protein Structure, Secondary Protein Structure, Tertiary Protein-Serine-Threonine Kinases - chemistry serine/threonine kinase 1 Staphylococcus aureus Staphylococcus aureus - enzymology Virulence Factors - chemistry |
| title | The Extended Conformation of the 2.9-Å Crystal Structure of the Three-PASTA Domain of a Ser/Thr Kinase from the Human Pathogen Staphylococcus aureus |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T22%3A15%3A06IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20Extended%20Conformation%20of%20the%202.9-%C3%85%20Crystal%20Structure%20of%20the%20Three-PASTA%20Domain%20of%20a%20Ser/Thr%20Kinase%20from%20the%20Human%20Pathogen%20Staphylococcus%20aureus&rft.jtitle=Journal%20of%20molecular%20biology&rft.au=Paracuellos,%20Patricia&rft.date=2010-12-17&rft.volume=404&rft.issue=5&rft.spage=847&rft.epage=858&rft.pages=847-858&rft.issn=0022-2836&rft.eissn=1089-8638&rft_id=info:doi/10.1016/j.jmb.2010.10.012&rft_dat=%3Cproquest_hal_p%3E812133534%3C/proquest_hal_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=812133534&rft_id=info:pmid/20965199&rft_els_id=S0022283610011095&rfr_iscdi=true |